研究者データベース

飯村 忠浩(イイムラ タダヒロ)
歯学研究院 口腔医学部門 口腔病態学分野
教授

基本情報

所属

  • 歯学研究院 口腔医学部門 口腔病態学分野

職名

  • 教授

学位

  • 博士(歯学)(東京医科歯科大学)

J-Global ID

研究キーワード

  • 骨格系の進化医学   口腔顎顔面の進化医学   神経骨格系の薬理学   代謝性骨疾患   骨格発生   骨代謝   

研究分野

  • ライフサイエンス / 常態系口腔科学 / 脊椎動物のボディプラン・骨格発生
  • ライフサイエンス / 常態系口腔科学 / 生化学・分子生物学・創薬育薬科学

職歴

  • 2019年03月 - 現在 北海道大学 大学院歯学研究院 教授
  • 2016年04月 - 2019年02月 愛媛大学 大学院医学系研究科 教授
  • 2015年04月 - 2019年02月 愛媛大学 学術支援センター(ADRES) 教授
  • 2015年01月 - 2019年02月 愛媛大学 プロテオサイエンスセンター(PROS) 教授
  • 2013年04月 - 2014年12月 愛媛大学 プロテオサイエンスセンター(PROS) 准教授
  • 2009年01月 - 2013年03月 東京医科歯科大学 グローバルCOE 特任准教授
  • 2008年04月 - 2008年12月 理化学研究所脳科学総合研究センター JST生命時空間情報PJ 研究員
  • 2004年12月 - 2008年03月 ストワーズ医学研究所 Olivier Pourquie 研究室 シニア研究員
  • 2004年10月 - 2005年03月 東京医科歯科大学 大学院硬組織薬理学分野 非常勤講師
  • 2002年08月 - 2004年11月 ストワーズ医学研究所 Olivier Pourquie 研究室 研究員
  • 1996年06月 - 2004年07月 東京医科歯科大学大学院 発生機構制御学講座・分子発生学分野 助手
  • 2000年11月 - 2002年07月 マルセイユ発生生物学研究所 Olivier Pourquie 研究室 研究員
  • 1995年07月 - 1996年05月 東京医科歯科大学 歯学部生化学教室 日本学術振興会特別研究員PD
  • 1995年04月 - 1995年06月 東京医科歯科大学 歯学部生化学教室 非常勤講師
  • 1992年04月 - 1995年03月 東京医科歯科大学 歯学部生化学教室 日本学術振興会特別研究員DC1

学歴

  • 1991年04月 - 1995年03月   東京医科歯科大学   大学院歯学研究科   生化学専攻
  • 1984年04月 - 1991年03月   北海道大学   歯学部   歯学科

所属学協会

  • 日本解剖学会   日本発生生物学会   日仏生物学会   口腔医科学フロンティア研究会   日本口腔科学会   日本薬理学会   日本顕微鏡学会   日本骨形態計測学会   歯科基礎医学会   日本骨代謝学会   

研究活動情報

論文

  • 田中智哉, 高尾亮子, 飯村忠浩
    日本骨形態計測学会雑誌 31 2 167 - 173 2021年07月01日 [査読有り][招待有り]
  • Takanori Sato, Aya Takakura, Ji-Won Lee, Kazuaki Tokunaga, Haruka Matsumori, Ryoko Takao-Kawabata, Tadahiro Iimura
    Microscopy (Oxford, England) 2021年06月08日 [査読有り]
     
    The lamellar structure of bone, which endows biomechanical rigidity to support the host organism is observed in mammals, including humans. It is therefore essential to develop a quantitative analysis to evaluate the lamellarity of bone, which would especially useful for the pharmacological evaluation of anti-osteoporotic drugs. This study applied a current system for the semi-automatic recognition of fluorescence signals to the analysis of un-decalcified bone sections from rat and monkey specimens treated with teriparatide (TPTD). Our analyses on bone formation pattern and collagen topology indicated that TPTD augmented bone lamellarity and bone collagen linearity, which were possibly associated with the recovery of collagen crosslinking, thus endowing bone rigidity.
  • Ji-Won Lee, In-Hee Lee, Takanori Sato, Sek Won Kong, Tadahiro Iimura
    Development, growth & differentiation 2021年02月17日 [査読有り]
     
    Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is a pandemic as of early 2020. Upon infection, SARS-CoV-2 attaches to its receptor of angiotensin-converting enzyme 2 (ACE2) on the surface of host cells and then is internalized into host cells via enzymatic machineries. This subsequently stimulates immune response factors. Since the host-immune response and severity of COVID-19 vary among individuals, genetic risk factors for severe COVID-19 cases have been investigated. Our research group recently conducted a survey of genetic variants among SARS-CoV-2-interacting molecules across populations, noting near absence of difference in allele frequency spectrum between populations in these genes. Recent genome-wide association studies have identified genetic risk factors for severe COVID-19 cases in a segment of chromosome 3 that involves six genes encoding three immune-regulatory chemokine receptors and another three molecules. The risk haplotype seemed to be inherited from Neanderthals, suggesting genetic adaptation against pathogens in modern human evolution. Therefore, SARS-CoV-2 uses highly conserved molecules as its virion interaction, whereas its immune-response appears to be genetically biased in individuals to some extent. We herein review the molecular process of SARS-CoV-2 infection with adding our further survey of genetic variants of its related immune effectors. We also discuss aspects of modern human evolution.
  • Ji-Won Lee, In-Hee Lee, Tadahiro Iimura, Sek Won Kong
    Bone research 9 1 11 - 11 2021年02月10日 [査読有り]
     
    Tissue-resident macrophages are highly specialized to their tissue-specific microenvironments, activated by various inflammatory signals and modulated by genetic and environmental factors. Osteoclasts and microglia are distinct tissue-resident cells of the macrophage lineage in bone and brain that are responsible for pathological changes in osteoporosis and Alzheimer's disease (AD), respectively. Osteoporosis is more frequently observed in individuals with AD compared to the prevalence in general population. Diagnosis of AD is often delayed until underlying pathophysiological changes progress and cause irreversible damages in structure and function of brain. As such earlier diagnosis and intervention of individuals at higher risk would be indispensable to modify clinical courses. Pleiotropy is the phenomenon that a genetic variant affects multiple traits and the genetic correlation between two traits could suggest a shared molecular mechanism. In this review, we discuss that the Pyk2-mediated actin polymerization pathway in osteoclasts and microglia in bone and brain, respectively, is the horizontal pleiotropic mediator of shared risk factors for osteoporosis and AD.
  • Ryuta Osumi, Ziyi Wang, Yoshihito Ishihara, Naoya Odagaki, Tadahiro Iimura, Hiroshi Kamioka
    Journal of Bone and Mineral Metabolism 2020年08月25日 [査読有り]
  • Tanaka T, Takao-Kawabata R, Takakura A, Shimazu Y, Nakatsugawa M, Ito A, Lee JW, Kawasaki, Iimura T
    Sci Rep. 10 1 5346  2020年03月24日 [査読有り][通常論文]
  • Yanagihara Y, Inoue K, Saeki N, Sawada Y, Yoshida S, Lee J, Iimura T, Imai Y
    Bone 122 93 - 100 2019年02月 [査読有り][通常論文]
  • Ishimaru Y, Oshima Y, Imai Y, Iimura T, Takanezawa S, Hino K, Miura H
    Molecules 23 23 pii: E3081  2018年11月 [査読有り][通常論文]
     
    Bone mineral density (BMD) is a commonly used diagnostic indicator for bone fracture risk in osteoporosis. Along with low BMD, bone fragility accounts for reduced bone quality in addition to low BMD, but there is no diagnostic method to directly assess the bone quality. In this study, we investigated changes in bone quality using the Raman spectroscopic technique. Sciatic neurectomy (NX) was performed in male C57/BL6J mice (NX group) as a model of disuse osteoporosis, and sham surgery was used as an experimental control (Sham group). Eight months after surgery, we acquired Raman spectral data from the anterior cortical surface of the proximal tibia. We also performed a BMD measurement and micro-CT measurement to investigate the pathogenesis of osteoporosis. Quantitative analysis based on the Raman peak intensities showed that the carbonate/phosphate ratio and the mineral/matrix ratio were significantly higher in the NX group than in the Sham group. There was direct evidence of alterations in the mineral content associated with mechanical properties of bone. To fully understand the spectral changes, we performed principal component analysis of the spectral dataset, focusing on the matrix content. In conclusion, Raman spectroscopy provides reliable information on chemical changes in both mineral and matrix contents, and it also identifies possible mechanisms of disuse osteoporosis.
  • Masayuki Morita, Hikaru Nagaoka, Edward H Ntege, Bernard N Kanoi, Daisuke Ito, Takahiro Nakata, Ji-Won Lee, Kazuaki Tokunaga, Tadahiro Iimura, Motomi Torii, Takafumi Tsuboi, Eizo Takashima
    Scientific reports 8 1 3696 - 3696 2018年02月27日 [査読有り][通常論文]
     
    Upon invasion, Plasmodium falciparum exports hundreds of proteins across its surrounding parasitophorous vacuole membrane (PVM) to remodel the infected erythrocyte. Although this phenomenon is crucial for the parasite growth and virulence, elucidation of precise steps in the export pathway is still required. A translocon protein complex, PTEX, is the only known pathway that mediates passage of exported proteins across the PVM. P. falciparum Parasitophorous Vacuolar protein 1 (PfPV1), a previously reported parasitophorous vacuole (PV) protein, is considered essential for parasite growth. In this study, we characterized PfPV1 as a novel merozoite dense granule protein. Structured illumination microscopy (SIM) analyses demonstrated that PfPV1 partially co-localized with EXP2, suggesting the protein could be a PTEX accessory molecule. Furthermore, PfPV1 and exported protein PTP5 co-immunoprecipitated with anti-PfPV1 antibody. Surface plasmon resonance (SPR) confirmed the proteins' direct interaction. Additionally, we identified a PfPV1 High-affinity Region (PHR) at the C-terminal side of PTP5 where PfPV1 dominantly bound. SIM analysis demonstrated an export arrest of PTP5ΔPHR, a PTP5 mutant lacking PHR, suggesting PHR is essential for PTP5 export to the infected erythrocyte cytosol. The overall results suggest that PfPV1, a novel dense granule protein, plays an important role in protein export at PV.
  • Yasumitsu Ishimaru, Yusuke Oshima, Yuuki Imai, Tadahiro Iimura, Sota Takanezawa, Kazunori Hino, Hiromasa Miura
    Progress in Biomedical Optics and Imaging - Proceedings of SPIE 10497 2018年 [査読有り][通常論文]
     
    To detect the bone quality loss in osteoporosis, we performed Raman spectroscopic analysis of sciatic nerve resection (NX) mice. Eight months after surgery, lower limbs were collected from the mice and fixed with 70% ethanol. Raman spectra of anterior cortical surface of the proximal tibia at 5 points in each bone were measured by RENISHAW inVia Raman Microscope. Excitation wave length was 785 nm. We also performed DXA and micro CT measurement to confirm the bone mineral density and bone microstructure in the osteoporotic model induced by sciatic nerve resection. In the result of Raman spectroscopy, we detected changes of Raman peak intensity ratio in carbonate/phosphate, mineral/combined proline and hydroxyproline and mineral/phenylalanine. In addition, in the result of micro CT, we found significant changes in VOX BV/TV, Trabecular number, thickness, cancellous bone mineral density, cortical thickness and cortical bone mineral density. The results suggest that not only the bone mineral density but also bone quality reduced in the NX mice. We conclude that Raman spectroscopy is a useful for bone quality assessment as a complementary technique for conventional diagnostics.
  • 骨組織の顕微鏡研究.
    飯村忠浩, 李 智媛
    顕微鏡 53 24 - 28 2018年 [査読有り][招待有り]
  • テリパラチドの高頻度投与は皮質骨空隙形成を誘導する.
    高倉綾, 李智媛, 山根宏志, 高尾亮子, 飯村忠浩
    日本骨形態計測学会雑誌 28 31 - 37 2018年 [査読有り][招待有り]
  • Michiko Yamashita, Kazuki Inoue, Noritaka Saeki, Maky Ideta-Otsuka, Yuta Yanagihara, Yuichiro Sawada, Iori Sakakibara, Jiwon Lee, Koichi Ichikawa, Yoshiaki Kamei, Tadahiro Iimura, Katsuhide Igarashi, Yasutsugu Takada, Yuuki Imai
    Development (Cambridge) 145 1 dev157412  2018年01月01日 [査読有り][通常論文]
     
    Transcriptional regulation can be tightly orchestrated by epigenetic regulators. Among these, ubiquitin-like with PHD and RING finger domains 1 (Uhrf1) is reported to have diverse epigenetic functions, including regulation of DNA methylation. However, the physiological functions of Uhrf1 in skeletal tissues remain unclear. Here, we show that limb mesenchymal cell-specific Uhrf1 conditional knockout mice (Uhrf1ΔLimb/ΔLimb) exhibit remarkably shortened long bones that have morphological deformities due to dysregulated chondrocyte differentiation and proliferation. RNA-seq performed on primary cultured chondrocytes obtained from Uhrf1ΔLimb/ΔLimb mice showed abnormal chondrocyte differentiation. In addition, integrative analyses using RNA-seq and MBD-seq revealed that Uhrf1 deficiency decreased genome-wide DNA methylation and increased gene expression through reduced DNA methylation in the promoter regions of 28 genes, including Hspb1, which is reported to be an IL1-related gene and to affect chondrocyte differentiation. Hspb1 knockdown in cKO chondrocytes can normalize abnormal expression of genes involved in chondrocyte differentiation, such as Mmp13. These results indicate that Uhrf1 governs cell type-specific transcriptional regulation by controlling the genome-wide DNA methylation status and regulating consequent cell differentiation and skeletal maturation.
  • Ji-Won Lee, Akiyoshi Hoshino, Kazuki Inoue, Takashi Saitou, Shunsuke Uehara, Yasuhiro Kobayashi, Satoshi Ueha, Kouji Matsushima, Akira Yamaguchi, Yuuki Imai, Tadahiro Iimura
    NATURE COMMUNICATIONS 8 1 2226  2017年12月 [査読有り][通常論文]
     
    C-C chemokine receptor 5 (CCR5) is a co-receptor of HIV. Epidemiological findings suggest that the functional loss of CCR5 is correlated with a lower incidence of bone-destructive diseases as well as of HIV transmission. However, it is not clear whether CCR5 is involved in regulation of the function of bone cells, in addition to that of immune cells. Here we show that blockade of CCR5 using specific antibodies impairs human osteoclast function in vitro. Ccr5-deficient (Ccr5(-/-)) mice presented with dysfunctional osteoclasts and were resistant to osteoporosis induced by receptor activator of nuclear factor kappa-B ligand (RANKL), which triggers osteoporosis independently of inflammatory and immunomodulatory pathways. Furthermore, Ccr5 deficiency impairs the cellular locomotion and bone-resorption activity of osteoclasts, which is associated with the disarrangement of podosomes and adhesion complex molecules including Pyk2. Overall, the data provides evidence that CCR5 has an essential role in bone-destructive conditions through the functional regulation of osteoclasts.
  • Masanori Koide, Yasuhiro Kobayashi, Teruhito Yamashita, Shunsuke Uehara, Midori Nakamura, B. Yukihiro Hiraoka, Yuki Ozaki, Tadahiro Iimura, Hisataka Yasuda, Naoyuki Takahashi, Nobuyuki Udagawa
    JOURNAL OF BONE AND MINERAL RESEARCH 32 10 2074 - 2086 2017年10月 [査読有り][通常論文]
     
    Bone formation is coupled to bone resorption throughout life. However, the coupling mechanisms are not fully elucidated. Using Tnfrsf11b-deficient (OPG(-/-)) mice, in which bone formation is clearly coupled to bone resorption, we found here that osteoclasts suppress the expression of sclerostin, a Wnt antagonist, thereby promoting bone formation. Wnt/-catenin signals were higher in OPG(-/-) and RANKL-transgenic mice with a low level of sclerostin. Conditioned medium from osteoclast cultures (Ocl-CM) suppressed sclerostin expression in UMR106 cells and osteocyte cultures. In vitro experiments revealed that osteoclasts secreted leukemia inhibitory factor (LIF) and inhibited sclerostin expression. Anti-RANKL antibodies, antiresorptive agents, suppressed LIF expression and increased sclerostin expression, thereby reducing bone formation in OPG(-/-) mice. Taken together, osteoclast-derived LIF regulates bone turnover through sclerostin expression. Thus, LIF represents a target for improving the prolonged suppression of bone turnover by antiresorptive agents. (C) 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
  • Hiroshi Yamane, Aya Takakura, Yukari Shimadzu, Toshiyuki Kodama, Ji-Won Lee, Yukihiro Isogai, Toshinori Ishizuya, Ryoko Takao-Kawabata, Tadahiro Iimura
    PLOS ONE 12 4 e0175329  2017年04月 [査読有り][通常論文]
     
    Teriparatide [human parathyroid hormone (1-34)], which exerts an anabolic effect on bone, is used for the treatment of osteoporosis in patients who are at a high risk for fracture. That the once-daily administration of teriparatide causes an increase in cortical porosity in animal models and clinical studies has been a matter of concern. However, it is not well documented that the frequency of administration and/or the total dose of teriparatide affect the cortical porosity. The present study developed 4 teriparatide regimens [20 mu g/kg/day (D20), 40 mu g/kg/day (D40), 140 mu g/kg/week (W140) and 280 mu g/kg/week (W280)] in the rabbit as a model animal with a well-developed Haversian system and osteons. The total weekly doses were equivalent in the low-dose groups (D20 and W140) and in the high-dose groups (D40 and W280). After the short-term (1 month) administration of TPDT, micro-CT, histomorphometry and three-dimensional second harmonic generation (3D-SHG) imaging to visualize the bone collagen demonstrated that daily regimens but not weekly regimens were associated with the significant development of cortical porosity and endosteal naive bone formation by marrow fibrosis. We concomitantly monitored the pharmacokinetics of the plasma teriparatide levels as well as the temporal changes in markers of bone formation and resorption. The analyses in the present study suggested that the daily repeated administration of teriparatide causes more deleterious changes in the cortical microarchitecture than the less frequent administration of higher doses. The findings of the present study may have some implications for use of teriparatide in clinical treatment.
  • Aya Takakura, Ji-Won Lee, Kyoko Hirano, Yukihiro Isogai, Toshinori Ishizuya, Ryoko Takao-Kawabata, Tadahiro Iimura
    BONE RESEARCH 5 17002  2017年04月 [査読有り][通常論文]
     
    To investigate whether the administration frequency of parathyroid hormone (PTH) is associated with the development of cortical porosity, this study established 15 dosage regimens of teriparatide [human PTH (1-34), TPTD] with four distinct concentrations and four distinct administration frequencies of TPTD to 16-week-old ovariectomized rats. Our analyses demonstrated that the bone mineral density, mechanical properties, and bone turnover were associated with the total amount of TPTD administered. Our observations further revealed that the cortical porosity was markedly developed as a result of an increased administration frequency with a lower concentration of total TPTD administration in our setting, although the highest concentration also induced cortical porosity. Deconvolution fluorescence tiling imaging on calcein-labeled undecalcified bone sections also demonstrated the development of cortical porosity to be closely associated with the bone site where periosteal bone formation took place. This site-specific cortical porosity involved intracortical bone resorption and an increased number and proximity of osteocytic lacunae, occasionally causing fused lacunae. Taken together, these findings suggested the involvement of local distinctions in the rate of bone growth that may be related to the site-specific mechanical properties in the development of cortical porosity induced by frequent and/or high doses of TPTD.
  • Ji-Won Lee, Tadahiro Iimura
    Japanese Dental Science Review 53 1 2 - 10 2017年02月01日 [査読有り][招待有り]
     
    Digitalized fluorescence images contain numerical information such as color (wavelength), fluorescence intensity and spatial position. However, quantitative analyses of acquired data and their validation remained to be established. Our research group has applied quantitative fluorescence imaging on tissue sections and uncovered novel findings in skeletal biomedicine and biodentistry. This review paper includes a brief background of quantitative fluorescence imaging and discusses practical applications by introducing our previous research. Finally, the future perspectives of quantitative fluorescence imaging are discussed.
  • Yasumitsu Ishimaru, Yusuke Oshima, Yuuki Imai, Tadahiro Iimura, Sota Takanezawa, Kazunori Hino, Hiromasa Miura
    Proceedings of SPIE - The International Society for Optical Engineering 10251 2017年 [査読有り][通常論文]
     
    To evaluate the bone quality in the osteoporosis, we generated sciatic nerve resection (NX) mice as an osteoporosis model and analyzed by Raman spectroscopy. Raman spectra were measured in anterior cortical surface of the proximal tibia at 5 points in each bone. After that, the samples were fixed with 70% ethanol. We then performed DXA and μCT measurement. Raman peak intensity ratios were significantly different between NX and Control. Those changes in the Raman peak intensity ratios may reflect loss of bone quality in the osteoporosis model. Raman spectroscopy is a promising technique for measuring the bone quality and bone strength.
  • Kenji Ogura, Tadahiro Iimura, Yuji Makino, Ayano Sugie-Oya, Aya Takakura, Ryoko Takao-Kawabata, Toshinori Ishizuya, Keiji Moriyama, Akira Yamaguchi
    Bone Reports 5 7 - 14 2016年12月01日 [査読有り][通常論文]
     
    Intermittent administration of human parathyroid hormone (1-34)[hPTH(1-34)] induces anabolic action on the bones. To understand the mechanism underlying the early phase of hPTH(1-34)-induced anabolic action, we investigated the expression profiles of osterix and sclerostin after short-term intermittent administration of hPTH(1-34) using immunohistochemistry in adult rats. In the cancellous bone, hPTH(1-34) administration greatly increased the number of osterix-positive cells in the bone marrow on day 1, but the cells gradually decreased on days 3 and 5. Injections of hPTH(1-34) induced no significant changes in the number of sclerostin-positive osteocytes in the cancellous bone. In the cortical bone, intermittent administration of hPTH(1-34) significantly reduced the number of sclerostin-positive osteocytes. The serum sclerostin level was downregulated and the osteocalcin level was upregulated on day 5 after intermittent administration of hPTH(1-34). Intermittent hPTH(1-34) injections increased osteoblast surface, osteoid thickness, and osteoid surface in cancellous bone, but not in cortical bone. This study suggested that the increase in osterix-positive osteoprogenitors in cancellous bone and the decrease in sclerostin-positive osteocytes in cortical bone play important roles in anabolic action on osteogenesis induced by short-term administration of hPTH(1-34).
  • 【筋と骨】 筋・骨格系の統合的な発生・発達におけるメカニカルストレスとHox遺伝子群
    飯村 忠浩
    THE BONE 29 3 265 - 271 (株)メディカルレビュー社 2015年10月 [査読無し][通常論文]
     
    筋・骨格系の組織発生・分化は個別に研究が進展し、それぞれの組織の発生由来や細胞系譜、分化誘導シグナル、分子レベルでの分化メカニズムの知見が集積されてきた。一方で、これらの組織を統合して、解剖学的に正しい位置に配置し機能ユニットとしての筋骨格系を成立させる機構に関しては、依然、不明な点が多い。最近の知見から、筋・骨格を結ぶ結合組織とそこに発現するHox遺伝子が、筋・骨格系の統合パターニングに重要であることが明らかになりつつある。(著者抄録)
  • 骨細胞の機能と形態のヘテロジェニティ
    李 智媛, 飯村 忠浩
    THE BONE 29 3 213 - 218 (株)メディカルレビュー社 2015年10月 [査読無し][通常論文]
  • 【顕微学的アプローチによる骨の細胞機能の解明】 軟骨・骨の組織病理学的解析における2光子励起顕微鏡の応用
    飯村 忠浩
    Clinical Calcium 25 10 1513 - 1520 (株)医薬ジャーナル社 2015年09月 [査読無し][通常論文]
     
    病理組織学的な手法は、医学研究や臨床において主要な地位を占めてきた。一方で、病理組織学的変化を定量することは、難しい面が多い。本稿では、2光子励起顕微鏡の基本原理について解説し、第2次高調波発生を応用した定量的な軟骨・骨の組織病理解析法について紹介する。(著者抄録)
  • 各種顕微鏡の進歩 さまざまな顕微鏡の革新的技術開発が拓く次世代多次元イメージング(第5回) 超解像顕微鏡
    飯村 忠浩
    病理と臨床 33 8 893 - 898 (株)文光堂 2015年08月 [査読無し][通常論文]
  • Atsuhiko Hikita, Tadahiro Iimura, Yusuke Oshima, Takashi Saitou, Shin Yamamoto, Takeshi Imamura
    BONE 76 5 - 17 2015年07月 [査読有り][通常論文]
     
    Bone modeling and remodeling are cellular events during which osteoblast lineage cells and osteoclasts interact. During these events, cells undergo drastic changes with time as they become differentiated. Their morphology, topology, and activity are affected by other cells and the extracellular matrices. Since the mechanisms underlying the cellular events of bone metabolism have not been elucidated, there is a need for systems to analyze these cellular networks and their microenvironments spatiotemporally at the cellular level. Here we report a novel in vitro system for reconstituting the bone cell network of osteoclasts, osteoblasts, and osteocytes in the mineralized nodule, allowing for observation of bone modeling and remodeling phenomena by 2-photon microscopy. Using this system, the change in morphology of osteoblasts from cuboidal to flat cells was observed and measured during the formation of mineralized nodules. Furthermore, the recruitment of osteoblasts to resorption pits and their replenishment by newly formed matrices were successfully observed, providing strong evidence for the coupling of bone resorption and bone formation at cellular level. During such remodeling cycle, flat osteoblasts that survived more than 7 weeks were recruited to resorption pits, where they became cuboidal osteoblasts that express osteocalcin. This novel system permitted the elucidation of cellular behavior during bone modeling and remodeling, and can be used to analyze cellular events involved in bone metabolism. (C) 2015 Elsevier Inc. All rights reserved.
  • Lin Zayar, Iimura Tadahiro, Kasugai Shohei, Yamaguchi Akira
    JOURNAL OF ORAL BIOSCIENCES 57 2 118 - 123 2015年05月 [査読有り][通常論文]
  • Ji-Won Lee, Tadahiro Iimura
    Journal of Oral Biosciences 57 2 76 - 79 2015年05月01日 [査読有り][通常論文]
     
    Background With colorful and high-contrast images, fluorescence imaging has long been a powerful tool used to confirm existing hypotheses or ideas suggested by other experimental approaches. Highlight Since data acquired by fluorescence imaging contain numerical values for spatio-temporal information as well as fluorescence intensities, quantitative fluorescence imaging is considered a robust tool that can provide novel insights by combining spatio-temporal information and quantitative analysis. Conclusion This short review presents the applications of quantitative fluorescence imaging in histological bone sections and its contribution to osteocyte biology. In osteocyte biology, fluorescence imaging has provided novel evidence on osteocytes being a heterogenic population both morphologically and functionally. Current direction and future applications of quantitative fluorescence imaging are also discussed in this review.
  • Zayar Lin, Tadahiro Iimura, Shohei Kasugai, Akira Yamaguchi
    Journal of Oral Biosciences 57 2 118 - 123 2015年05月01日 [査読有り][通常論文]
     
    Objective Transplantation of non-osteogenic cells that express osteoinductive factors is a potential strategy for cell-mediated bone regenerative therapy. In this study, we investigated the effects of transplantation of canine oral mucosal fibroblasts (COFs) overexpressing human bone morphogenetic protein (BMP-2) on bone regeneration. Methods COFs isolated from canine buccal mucosa were transfected with BMP-2-containing pCEP4 or pcDNA vectors by electroporation. The effects of BMP-2 on osteoblast differentiation were assessed by measuring the activity of alkaline phosphatase and the expression of osterix and Runx2 in BMP-2-overexpressing COFs. BMP-2-overexpressing COFs were transplanted into bone defects created on calvariae of athymic mice. Bone regeneration was assessed by micro-CT analysis and histological examination. The fates of transplanted cells were traced on histological sections by monitoring the expression of green fluorescence protein (GFP), which was cotransfected with BMP-2. Results Transfection with pcDNA-BMP2 or pCEP4-BMP2 increased the numbers of ALP-positive cells and the mRNA expression levels of Runx2 and Osterix. Micro-CT and histological analyses revealed that transplantation of COFs transfected with pCEP4-BMP2 or pcDNA-BMP2 induced regeneration of calvarial bone defects, while COFs transfected with control pCEP4 or pcDNA plasmids failed to achieve bone regeneration. The histological experiments tracing GFP expression revealed that COFs transfected with pCEP4-BMP2 or pcDNA-BMP2 differentiated into osteoblasts and osteocytes in regions of regenerating bone. Conclusions Transplanted COFs that overexpressed BMP-2 differentiated into osteoblasts and osteocytes during bone regeneration, and participated in new bone formation.
  • 骨細胞のin situ蛍光計測による機能解析
    飯村 忠浩
    O.li.v.e. 5 2 123 - 123 (株)メディカルレビュー社 2015年05月 [査読無し][通常論文]
  • Ji-Won Lee, Midori Asai, Sang-Kyung Jeon, Tadahiro Iimura, Takayuki Yonezawa, Byung-Yoon Cha, Je-Tae Woo, Akira Yamaguchi
    MOLECULAR NUTRITION & FOOD RESEARCH 59 3 386 - 400 2015年03月 [査読有り][通常論文]
     
    Scope: Bone homeostasis is ensured by the balance between bone formation and resorption. Thus, control of the recruitment, proliferation, and differentiation of bone cells is essential to maintain bone mass. The aim of this study was to elucidate the effects of rosmarinic acid as a potential therapeutic agent on bone metabolism using bone cells and a mouse model. Methods and results: Rosmarinic acid increased alkaline phosphatase activity and induced mineralization in osteoblasts. Addition of rosmarinic acid to cultures of calvarial osteoblastic cells prepared from T-cell factor/beta-catenin TOP-GAL mutant mice strongly induced the expression of LacZ and promoted stabilization of beta-catenin in the cytoplasm of ST2 cells, suggesting that rosmarinic acid affects the canonical Wnt signaling pathway. Moreover, rosmarinic acid inhibited not only osteoclast formation in cocultures of mouse bone marrow cells and osteoblasts, but also receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastic differentiation in bone marrow-derived macrophages. RANKL-induced p38 mitogen-activated protein kinase and the expression of nuclear factor of activated T cell, c-Jun, and c-Fos were inhibited by rosmarinic acid in bone marrow macrophages. Finally, we confirmed that rosmarinic acid improved bone mass in a soluble RANKL-induced bone loss mouse model. Conclusion: Rosmarinic acid has dual regulatory effects on bone metabolism and may control the bone functions by controlling osteoblastic and osteoclastic differentiation.
  • Nicolas Denans, Tadahiro Iimura, Olivier Pourquie
    ELIFE 4 2015年02月 [査読有り][通常論文]
     
    In vertebrates, the total number of vertebrae is precisely defined. Vertebrae derive from embryonic somites which are continuously produced posteriorly from the presomitic mesoderm (PSM) during body formation. We show that in the chicken embryo, activation of posterior Hox genes (paralogs 9-13) in the tail-bud correlates with the slowing-down of axis elongation. Our data indicate that a subset of progressively more posterior Hox genes, which are collinearly activated in vertebral precursors, repress Wnt activity with increasing strength. This leads to a graded repression of the Brachyury/T transcription factor, reducing mesoderm ingression and slowing down the elongation process. Due to the continuation of somite formation, this mechanism leads to the progressive reduction of PSM size. This ultimately brings the retinoic acid (RA)-producing segmented region in close vicinity to the tail bud, potentially accounting for the termination of segmentation and axis elongation.
  • Hiroshi Kiyomatsu, Yusuke Oshima, Takashi Saitou, Tsuyoshi Miyazaki, Atsuhiko Hikita, Hiromasa Miura, Tadahiro Iimura, Takeshi Imamura
    BIOMEDICAL OPTICS EXPRESS 6 2 405 - 420 2015年02月 [査読有り][通常論文]
     
    Osteoarthritis (OA) restricts the daily activities of patients and significantly decreases their quality of life. The development of noninvasive quantitative methods for properly diagnosing and evaluating the process of degeneration of articular cartilage due to OA is essential. Second harmonic generation (SHG) imaging enables the observation of collagen fibrils in live tissues or organs without staining. In the present study, we employed SHG imaging of the articular cartilage in OA model mice ex vivo. Consequently, three-dimensional SHG imaging with successive image processing and statistical analyses allowed us to successfully characterize histopathological changes in the articular cartilage consistently confirmed on histological analyses. The quantitative SHG imaging technique presented in this study constitutes a diagnostic application of this technology in the setting of OA. (C) 2015 Optical Society of America
  • Shigehiro Koga, Yusuke Oshima, Atsuhiko Hikita, Koichi Sato, Motohira Yoshida, Yuji Yamamoto, Tadahiro Iimura, Yuji Watanabe, Takeshi Imamura
    Progress in Biomedical Optics and Imaging - Proceedings of SPIE 9339 2015年 [査読有り][通常論文]
     
    We developed a near infrared fluorophore-conjugated anti-Carcinoembryonic antigen (CEA) antibody for mice bearing tumor of CEA expressing cells, and demonstrated in vivo optical imaging by macro zoom microscopy. In the result, tumors of CEA-expressing cancer cells were specifically detected in vivo. Furthermore, cancer-specific fluorescence images were acquired at subcellular level in vivo by two-photon microscopy. In preclinical applications, the lymph node micrometastasis was also successfully visualized by two-photon microscopy. These results suggest that two-photon excitation microscopy in combination with an immunoconjugated probe could be widely adapted to cancer detection in clinical settings.
  • Yusuke Oshima, Tadahiro Iimura, Takashi Saitou, Takeshi Imamura
    PHOTONIC THERAPEUTICS AND DIAGNOSTICS XI 9303 2015年 [査読有り][通常論文]
     
    Osteoporosis is a major bone disease that connotes the risk of fragility fractures resulting from alterations to bone quantity and/or quality to mechanical competence. Bone strength arises from both bone quantity and quality. Assessment of bone quality and bone quantity is important for prediction of fracture risk. In spite of the two factors contribute to maintain the bone strength, only one factor, bone mineral density is used to determine the bone strength in the current diagnosis of osteoporosis. On the other hand, there is no practical method to measure chemical composition of bone tissue including hydroxyapatite and collagen non-invasively. Raman spectroscopy is a powerful technique to analyze chemical composition and material properties of bone matrix non-invasively. Here we demonstrated Raman spectroscopic analysis of the bone matrix in osteoporosis model rat. Ovariectomized (OVX) rat was made and the decalcified sections of tibias were analyzed by a Raman microscope. In the results, Raman bands of typical collagen appeared in the obtained spectra. Although the typical mineral bands at 960 cm(-1) (Phosphate) was absent due to decalcified processing, we found that Raman peak intensities of amide I and C-C stretching bands were significantly different between OVX and sham-operated specimens. These differences on the Raman spectra were statistically compared by multivariate analyses, principal component analysis (PCA) and liner discrimination analysis (LDA). Our analyses suggest that amide I and C-C stretching bands can be related to stability of bone matrix which reflects bone quality.
  • 超域ネットワーク型」生命医学研究支援体制の構築に向けて.
    飯村 忠浩
    愛媛ジャーナル 29 75 - 77 2015年 [査読無し][招待有り]
  • Yuriko Nishiyama, Tsutomu Matsumoto, Ji-Won Lee, Takashi Saitou, Takeshi Imamura, Keiji Moriyama, Akira Yamaguchi, Taclahiro Iimura
    ARCHIVES OF ORAL BIOLOGY 60 1 45 - 54 2015年01月 [査読有り][通常論文]
     
    Objective: Mechanical loading on the bone is sensed by osteocytes. Sclerostin is a molecule secreted by osteocytes that is downregulated by mechanical loading; therefore, its expression level is a potent sensor that indicates the spatial transduction of biomechanical properties in bone. This study applied macroconfocal microscopy to observe the spatial response of alveolar bone to orthodontic forces after immunofluorescence using anti-sclerostin antibodies. Design: Orthodontic tooth movement with the Ni-Ti closed-coil spring was applied between the upper bilateral incisors and the left first molar of mice. Four days after this application, the animals were subjected to multimodal confocal fluorescence imaging analyses. Results: Obvious downregulation of sclerotin in the osteocytic lacuna-canalicular system (LCS) was observed specifically in tensile sites of alveolar bone. Confocal-based three-dimensional fluorescence morphometry further quantitatively demonstrated that the distribution and expression of sclerostin in the tensile sites was significantly reduced compared to that observed in the corresponding control sites. Interestingly, the levels of sclerotin signals in the compression sites were significantly higher than those observed in the control sites, although the distribution of sclerotin was not significantly different. Conclusions: Our observations suggest that spatial changes in the level and distribution of sclerostin in the alveolar LCS trigger successive bone remodelling due to orthodontic tooth movement. The multimodal confocal imaging analyses applied in this work will enhance comprehensive understanding regarding the spatial regulation of molecules of interest from the tissue to the cellular level. (C) 2014 Elsevier Ltd. All rights reserved.
  • Yusuke Oshima, Tadahiro Iimura, Takashi Saitou, Takeshi Imamura
    Progress in Biomedical Optics and Imaging - Proceedings of SPIE 9303 2015年 [査読無し][通常論文]
     
    Osteoporosis is a major bone disease that connotes the risk of fragility fractures resulting from alterations to bone quantity and/or quality to mechanical competence. Bone strength arises from both bone quantity and quality. Assessment of bone quality and bone quantity is important for prediction of fracture risk. In spite of the two factors contribute to maintain the bone strength, only one factor, bone mineral density is used to determine the bone strength in the current diagnosis of osteoporosis. On the other hand, there is no practical method to measure chemical composition of bone tissue including hydroxyapatite and collagen non-invasively. Raman spectroscopy is a powerful technique to analyze chemical composition and material properties of bone matrix non-invasively. Here we demonstrated Raman spectroscopic analysis of the bone matrix in osteoporosis model rat. Ovariectomized (OVX) rat was made and the decalcified sections of tibias were analyzed by a Raman microscope. In the results, Raman bands of typical collagen appeared in the obtained spectra. Although the typical mineral bands at 960 cm-1 (Phosphate) was absent due to decalcified processing, we found that Raman peak intensities of amide I and C-C stretching bands were significantly different between OVX and sham-operated specimens. These differences on the Raman spectra were statistically compared by multivariate analyses, principal component analysis (PCA) and liner discrimination analysis (LDA). Our analyses suggest that amide I and C-C stretching bands can be related to stability of bone matrix which reflects bone quality.
  • Mayu Sugiyama, Takashi Saitou, Hiroshi Kurokawa, Asako Sakaue-Sawano, Takeshi Imamura, Atsushi Miyawaki, Tadahiro Iimura
    PLOS COMPUTATIONAL BIOLOGY 10 12 e1003957  2014年12月 [査読有り][通常論文]
     
    In multicellular organism development, a stochastic cellular response is observed, even when a population of cells is exposed to the same environmental conditions. Retrieving the spatiotemporal regulatory mode hidden in the heterogeneous cellular behavior is a challenging task. The G1/S transition observed in cell cycle progression is a highly stochastic process. By taking advantage of a fluorescence cell cycle indicator, Fucci technology, we aimed to unveil a hidden regulatory mode of cell cycle progression in developing zebrafish. Fluorescence live imaging of Cecyil, a zebrafish line genetically expressing Fucci, demonstrated that newly formed notochordal cells from the posterior tip of the embryonic mesoderm exhibited the red (G1) fluorescence signal in the developing notochord. Prior to their initial vacuolation, these cells showed a fluorescence color switch from red to green, indicating G1/S transitions. This G1/S transition did not occur in a synchronous manner, but rather exhibited a stochastic process, since a mixed population of red and green cells was always inserted between newly formed red (G1) notochordal cells and vacuolating green cells. We termed this mixed population of notochordal cells, the G1/S transition window. We first performed quantitative analyses of live imaging data and a numerical estimation of the probability of the G1/S transition, which demonstrated the existence of a posteriorly traveling regulatory wave of the G1/S transition window. To obtain a better understanding of this regulatory mode, we constructed a mathematical model and performed a model selection by comparing the results obtained from the models with those from the experimental data. Our analyses demonstrated that the stochastic G1/S transition window in the notochord travels posteriorly in a periodic fashion, with doubled the periodicity of the neighboring paraxial mesoderm segmentation. This approach may have implications for the characterization of the pathophysiological tissue growth mode.
  • Shigehiro Koga, Yusuke Oshima, Naoki Honkura, Tadahiro Iimura, Kenji Kameda, Koichi Sato, Motohira Yoshida, Yuji Yamamoto, Yuji Watanabe, Atsuhiko Hikita, Takeshi Imamura
    CANCER SCIENCE 105 10 1299 - 1306 2014年10月 [査読有り][通常論文]
     
    Recently, there has been growing interest in applying fluorescence imaging techniques to the study of various disease processes and complex biological phenomena in vivo. To apply these methods to clinical settings, several groups have developed protocols for fluorescence imaging using antibodies against tumor markers conjugated to fluorescent substances. Although these probes have been useful in macroscopic imaging, the specificity and sensitivity of these methods must be improved to enable them to detect micro-lesions in the early phases of cancer, resulting in better treatment outcomes. To establish a sensitive and highly specific imaging method, we used a fluorophore-conjugated anti-carcinoembryonic antigen (CEA) antibody to perform macroscopic and microscopic in vivo imaging of inoculated cancer cells expressing GFP with or without CEA. Macroscopic imaging by fluorescence zoom microscopy revealed that bio-conjugation of Alexa Fluor 594 to the anti-CEA antibody allowed visualization of tumor mass consisting of CEA-expressing human cancer cells, but the background levels were unacceptably high. In contrast, microscopic imaging using a two-photon excitation microscope and the same fluorescent antibody resulted in subcellular-resolution imaging that was more specific and sensitive than conventional imaging using a fluorescence zoom microscope. These results suggest that two-photon excitation microscopy in conjunction with fluorophore-conjugated antibodies could be widely adapted to detection of cancer-specific cell-surface molecules, both in cancer research and in clinical applications.
  • 【Molecular Imaging 2014 分子イメージングはどこまで進んだか】 分子イメージングの最新動向 光イメージングの最新動向 バイオイメージングの現状と展望
    今村 健志, 疋田 温彦, 大嶋 佑介, 飯村 忠浩
    INNERVISION 29 7 39 - 41 (株)インナービジョン 2014年06月 [査読無し][通常論文]
     
    最近のライフサイエンス研究分野の動向として、細胞、動物やヒトが生きたままで、タンパク質などの生体分子の動態や機能を解析することが強く求められるようになってきた。生命現象をより深く理解し、病気の原因を明らかにし、治療法を研究するためには、タンパク質などの生体分子の体内での時空間的動態や機能を解析する必要があり、これまでの生化学実験技術や分子生物学実験技術に加え、動物が生きたまま経時的に細胞や分子の動態を解析できるバイオイメージング技術が必要である。いまやバイオイメージングは、ライフサイエンス研究分野に必要不可欠な技術になっている。本稿では、バイオイメージングの現状と展望について、特に生体蛍光イメージングを中心に、われわれのデータを紹介しながら問題点を洗い出し、将来展望について考察する。(著者抄録)
  • 【骨バイオイメージング】 次世代骨バイオイメージング ラマン分光法による骨組織の分子計測と骨質評価への応用
    大嶋 佑介, 飯村 忠浩, 疋田 温彦, 今村 健志
    THE BONE 28 2 197 - 202 (株)メディカルレビュー社 2014年06月 [査読無し][通常論文]
     
    骨組織は、リン酸カルシウム結晶であるヒドロキシアパタイトとコラーゲン線維を多く含む硬組織であり、骨強度を評価する上で無機質の含有量すなわち骨密度の計測だけでなくコラーゲン架橋の状態を知ることが重要である。既存の診断技術ではコラーゲン架橋などを非侵襲的に計測することは困難であるが、ラマン分光法を用いることにより骨基質の分子を直接計測することが可能であり、将来的には骨質評価法としての実用化が期待される。(著者抄録)
  • 【骨バイオイメージング】 次世代骨バイオイメージング 2光子励起顕微鏡を用いた骨・軟骨組織イメージング
    疋田 温彦, 大嶋 佑介, 飯村 忠浩, 今村 健志
    THE BONE 28 2 191 - 195 (株)メディカルレビュー社 2014年06月 [査読無し][通常論文]
     
    骨をはじめとする生体組織のイメージングにおいては、光の吸収、散乱、各種収差が問題となる。光の散乱や各種収差を克服するため、励起光源の長波長化、補償光学技術の応用が試みられている。また、2光子励起顕微鏡では第2次高調波発生(second harmonic generation:SHG)によりコラーゲンの無染色イメージングが可能であり、骨・軟骨の質的診断への応用が期待される。(著者抄録)
  • 【骨バイオイメージング】 静的イメージング 骨細胞の3次元解析
    飯村 忠浩
    THE BONE 28 2 165 - 172 (株)メディカルレビュー社 2014年06月 [査読無し][通常論文]
     
    骨細胞は骨に加わる荷重のメカノセンサーとして働き、その近傍で骨リモデリングに関与していることが明らかになってきた。骨細胞のメカノセンシングシステムは、細胞突起を介した骨細胞間のネットワーク(骨細胞ネットワーク)と骨小腔・細管系との相互作用として伝えられると考えられ、その理解にはin vitroあるいはin situでのトポロジカル(3次元形態学的)な観察が重要である。本稿では、骨細胞および骨小腔の微細構造の可視化・定量化に関する研究について概説する。(著者抄録)
  • 【骨代謝 つくり、壊し、変える-そのメカニズムと最新治療 分子機構から骨粗鬆症・リウマチなど骨疾患への応用まで】(第I部) 骨代謝制御機構を知る (第3章)骨をみる イメージングの現状と展望 骨細胞の形態と機能ダイナミズムの可視化・定量化
    飯村 忠浩
    実験医学 32 7 1067 - 1073 (株)羊土社 2014年05月 [査読無し][通常論文]
     
    骨細胞は骨組織に加わる機械的負荷の受容細胞として、またリン酸代謝にかかわる外分泌細胞としても重要な役割を担っており、骨代謝の中心的プレーヤーとして認識されるようになってきた。骨細胞の機能は、その三次元構造と密接に関係しているため、その理解にはin vitroあるいはin situでの観察が重要である。本稿では、骨細胞ネットワークの微細構造解析および蛍光イメージングによる可視化・定量化および蛍光ライブイメージングによる機能解析に関する研究について概説する。(著者抄録)
  • Ji-Won Lee, Akira Yamaguchi, Tadahiro Iimura
    JOURNAL OF BONE AND MINERAL RESEARCH 29 S171 - S171 2014年02月 [査読有り][通常論文]
  • Lee JW, Yamaguchi A, Iimura T
    BoneKEy reports 3 543  2014年 [査読有り][通常論文]
  • Imamura T, Hikita A, Oshima Y, Iimura T
    Clinical calcium 23 12 1767 - 1773 2013年12月 [査読有り][通常論文]
  • 【骨・軟骨疾患と再生】 骨・軟骨組織の生体光イメージング
    今村 健志, 疋田 温彦, 大嶋 佑介, 飯村 忠浩
    Clinical Calcium 23 12 1767 - 1773 (株)医薬ジャーナル社 2013年11月 [査読無し][通常論文]
     
    近年、動物が生きたままの状態で、多様な生命現象を解析できるintravital optical imaging(生体光イメージング)の技術が急速に発展しつつある。特に新しい蛍光タンパク質や蛍光有機小分子の発見や改良、2光子励起顕微鏡など蛍光検出機器の性能の飛躍的向上や画像処理ソフトウェアの開発により、これまで蛍光技術の応用が困難であった骨・軟骨組織においてもその応用が可能になりつつある。本稿では、生体光イメージング技術の最近の進歩とその骨・軟骨組織解析への応用について、われわれのデータを紹介しながら、現状とその問題点、さらにその将来や臨床応用の可能性について議論したい。(著者抄録)
  • 【骨細胞:骨を制御する司令塔】 骨細胞ネットワークのイメージング
    飯村 忠浩
    THE BONE 27 3 271 - 277 (株)メディカルレビュー社 2013年08月 [査読無し][通常論文]
     
    骨細胞は骨基質内に多数の細い細胞突起を張り巡らせて細胞間ネットワークを構築し、骨芽細胞や破骨細胞の機能を調節している。また、骨細胞は骨組織に加わる機械的負荷の受容細胞としても重要な役割を担っている。そのため、骨組織の生理的維持機構や病的な動態を把握するためには、骨細胞および骨細胞ネットワークの詳細な形態や動態を、骨の機能と関連させて理解しておくことが重要である。本稿では、筆者らが行ってきた蛍光三次元イメージングによる形態計測に関する研究について概説する。(著者抄録)
  • Rieko Tanabe, Mayu Haraikawa, Natsuko Sogabe, Aoi Sugimoto, Yuka Kawamura, Satoshi Takasugi, Masashi Nagata, Ayako Nakane, Akira Yamaguchi, Tadahiro Iimura, Masae Goseki-Sone
    JOURNAL OF NUTRITIONAL BIOCHEMISTRY 24 6 1000 - 1007 2013年06月 [査読有り][通常論文]
     
    The current study compared the effects of milk, yogurt or whey on the bone strength, body composition and serum biomarkers. Forty 12-week-old female Sprague-Dawley rats were ovariectomized (OVX), and another nine rats received a sham operation (Sham-Cont). After a 1-week recovery period, the OVX rats were divided into four dietary groups: OVX-control group (OVX-Cont), 17% skimmed milk powder diet group (OVX-Milk), 17% powdered fermented milk diet group (OVX-Yogurt) and 12% whey powder and 6% whey protein extract diet group (OVX-Whey) (n=10 in each group). The protein, nitrogen, fat, calcium and phosphorus contents of the experimental diets were adjusted to be similar to the control diet (AIN-93M). Eighty-four days after the beginning of the experimental diet, the total bone mineral density and bone mineral contents of lumbar vertebrae were significantly higher in the OVX-Milk and OVX-Whey groups than in the OVX-Cont group. Furthermore, the level of 1alpha, 25-dihydroxyvitamin D-3 [1alpha, 25(OH)(2)D-3] was significantly lower, while the serum level of FGF23 was significantly higher in the OVX-Milk, OVX-Yogurt and OVX-Whey groups than in the OVX-Cont group. These findings suggest that milk and the dairy products could improve bone metabolism in a postmenopausal animal model at least partly through changing the balance between 1alpha, 25(OH)(2)D-3 and FGF23. (C) 2013 Elsevier Inc. All rights reserved.
  • Kiyoshi Sato, Ji-Won Lee, Kei Sakamoto, Tadahiro Iimura, Kou Kayamori, Hisataka Yasuda, Masanobu Shindoh, Masako Ito, Ken Omura, Akira Yamaguchi
    Am. J. Pathol. 182 5 1890 - 1899 2013年05月 [査読有り][通常論文]
     
    The molecular mechanisms underlying bone destruction by invading oral cancer are not well understood. Using IHC, we demonstrated that receptor activator of nuclear factor-κB ligand (RANKL)-positive fibroblasts and cancer cells were located at sites of bone invasion in human oral cancers. HSC3 and HO-1-N-1, human oral cancer cell lines, expressed RANKL and stimulated Rankl expression in the UAMS-32 murine osteoblastic cell line. We discriminated the roles of RANKL synthesized by stromal cells and cancer cells in cancer-associated bone resorption by using species-specific RANKL antibodies against murine RANKL and human RANKL, respectively. Osteoclastogenesis induced by the conditioned medium of HSC3 and HO-1-N-1 cells in a co-culture of murine bone marrow cells and UAMS-32 cells was inhibited by the addition of antibodies against either mouse or human RANKL. HSC3-induced bone destruction was greatly inhibited by the administration of anti-mouse RANKL antibody in a xenograft model. HO-1-N-1-induced bone destruction was inhibited by the administration of either anti-mouse or anti-human RANKL antibody. Bone destruction induced by the transplantation of human RANKL-overexpressing cells
  • Kiyoshi Sato, Ji-Won Lee, Kei Sakamoto, Tadahiro Iimura, Kou Kayamori, Hisataka Yasuda, Masanobu Shindoh, Masako Ito, Ken Omura, Akira Yamaguchi
    AMERICAN JOURNAL OF PATHOLOGY 182 5 1890 - 1899 2013年05月 [査読有り][通常論文]
     
    The molecular mechanisms underlying bone destruction by invading oral cancer are not well understood. Using IHC, we demonstrated that receptor activator of nuclear factor-kappa B Ligand (RANKL)-positive fibroblasts and cancer cells were Located at sites of bone invasion in human oral cancers. HSC3 and HO-1-N-1, human oral cancer cell Lines, expressed RANKL and stimulated Rankl expression in the UAMS-32 murine osteoblastic cell Line. We discriminated the roles of RANKL synthesized by stromal cells and cancer cells in cancer-associated bone resorption by using species-specific RANKL antibodies against murine RANKL and human RANKL, respectively. Osteoclastogenesis induced by the conditioned medium of HSC3 and HO-1-N-1 cells in a co-culture of murine bone marrow cells and UAMS-32 cells was inhibited by the addition of antibodies against either mouse or human RANKL. HSC3-induced bone destruction was greatly inhibited by the administration of anti-mouse RANKL antibody in a xenograft model. HO-1-N-1 induced bone destruction was inhibited by the administration of either anti-mouse or anti-human RANKL antibody. Bone destruction induced by the transplantation of human RANKL-overexpressing cells (HSC3-R2) was greatly inhibited by the injection of anti-human RANKL antibody. The present study revealed that RANKL produced by both stomal and cancer cells is involved in oral cancer induced osteoclastic bone resorption. These results provide important information for understanding the cellular and molecular basis of cancer-associated bone destruction and the mechanism of action underlying RANKL antibody (denosumab) therapy.
  • T. Matsumoto, T. Iimura, K. Ogura, K. Moriyama, A. Yamaguchi
    Journal of Dental Research 92 4 340 - 345 2013年04月 [査読有り][通常論文]
     
    We investigated the roles of osteocytes in osteoclastic bone resorption during orthodontic tooth movement using the transgenic mice in which osteocytes can be specifically ablated. Because these transgenic mice express the receptor for diphtheria toxin on the cell surfaces of osteocytes, the injection of diphtheria toxin can ablate their osteocytes in vivo. Injection of diphtheria toxin into the transgenic mice significantly increased the number of ablated osteocytes in alveolar bone compared with that in wild-type mice with or without diphtheria toxin injection. Increased numbers of ablated osteocytes were observed from day 4 to day 12 after the injection in alveolar bones as well as in cortical bone of the tibiae. We applied the orthodontic force 4 days after the injection of diphtheria toxin, and the distance of tooth movement on day 12 was significantly smaller in transgenic mice than that in control mice. The numbers of osteoclasts and the quantity of eroded bone surface at the compression site were significantly reduced in the transgenic mice injected with diphtheria toxin than in control mice. These results provide in vivo demonstration of osteocyte involvement in osteoclastic bone resorption during orthodontic tooth movement. © 2013 International & American Associations for Dental Research.
  • Satoshi Shimozono, Tadahiro Iimura, Tetsuya Kitaguchi, Shin-ichi Higashijima, Atsushi Miyawaki
    NATURE 496 7445 363 - + 2013年04月 [査読有り][通常論文]
     
    In vertebrate development, the body plan is determined by primordial morphogen gradients that suffuse the embryo. Retinoic acid (RA) is an important morphogen involved in patterning the anterior-posterior axis of structures, including the hindbrain(1-6) and paraxial mesoderm(7,8). RA diffuses over long distances, and its activity is spatially restricted by synthesizing and degrading enzymes(9). However, gradients of endogenous morphogens in live embryos have not been directly observed; indeed, their existence, distribution and requirement for correct patterning remain controversial(10). Here we report a family of genetically encoded indicators for RA that we have termed GEPRAs (genetically encoded probes for RA). Using the principle of fluorescence resonance energy transfer we engineered the ligand-binding domains of RA receptors to incorporate cyan-emitting and yellow-emitting fluorescent proteins as fluorescence resonance energy transfer donor and acceptor, respectively, for the reliable detection of ambient free RA. We created three GEPRAs with different affinities for RA, enabling the quantitative measurement of physiological RA concentrations. Live imaging of zebrafish embryos at the gastrula and somitogenesis stages revealed a linear concentration gradient of endogenous RA in a two-tailed source-sink arrangement across the embryo. Modelling of the observed linear RA gradient suggests that the rate of RA diffusion exceeds the spatiotemporal dynamics of embryogenesis, resulting in stability to perturbation. Furthermore, we used GEPRAs in combination with genetic and pharmacological perturbations to resolve competing hypotheses on the structure of the RA gradient during hindbrain formation and somitogenesis. Live imaging of endogenous concentration gradients across embryonic development will allow the precise assignment of molecular mechanisms to developmental dynamics and will accelerate the application of approaches based on morphogen gradients to tissue engineering and regenerative medicine.
  • Yuji Makino, Yu Takahashi, Rieko Tanabe, Yoshihiro Tamamura, Takashi Watanabe, Mayu Haraikawa, Miwako Hamagaki, Kenji Hata, Jun Kanno, Toshiyuki Yoneda, Yumiko Saga, Masae Goseki-Sone, Kazuo Kaneko, Akira Yamaguchi, Tadahiro Iimura
    BONE 53 1 248 - 258 2013年03月 [査読有り][通常論文]
     
    Spondylocostal dysostosis (SCDO) is a genetic disorder characterized by severe malformation of the axial skeleton. Mesp2 encodes a basic helix-loop-helix type transcription factor that is required for somite formation. Its human homologue, Mesp2, is a gene affected in patients with SCDO and a related vertebral disorder, spondylothoracic dysostosis (STDO). This work investigated how the loss of Mesp2 affects axial skeleton development and causes the clinical features of SCDO and STDO. We first confirmed, by three-dimensional computed tomography scanning, that Mesp2-null mice exhibited mineralized tissue patterning resembling the radiological features of SCDO and STDO. Histological observations and in situ hybridization probing for extracellular matrix molecules demonstrated that the developing vertebral bodies in Mesp2-null mice were extensively fused with rare insertions of intervertebral tissue. Unexpectedly, the intervertebral tissues were mostly fused longitudinally in the vertebral column, instead of exhibiting extended formation, as was expected based on the caudalized properties of Mesp2-null somite derivatives. Furthermore, the differentiation of vertebral body chondrocytes in Mesp2-null mice was spatially disordered and largely delayed, with an increased cell proliferation rate. The quantitative three-dimensional immunofluorescence image analyses of phospho-Smad2 and -Smad1/5/8 revealed that these chondrogenic phenotypes were associated with spatially disordered inputs of TGF-beta and BMP signaling in the Mesp2-null chondrocytes, and also demonstrated an amorphous arrangement of cells with distinct properties. Furthermore, a significant delay in ossification in Mesp2-null vertebrae was observed by peripheral quantitative computed tomography. The current observations of the spatiotemporal disorder of vertebral organogenesis in the Mesp2-null mice provide further insight into the pathogenesis of SCDO and STDO, and the physiological development of the axial skeleton. (C) 2012 Elsevier Inc. All rights reserved.
  • 生後骨発達におけるSclerostin発現分布の時空間的変化 蛍光イメージングによる骨組織のグローカルな観察
    渡辺 高, 原田 清, 山口 朗, 飯村 忠浩
    THE BONE 27 1 5 - 10 (株)メディカルレビュー社 2013年03月 [査読無し][通常論文]
  • Akiyoshi Hoshino, Satoshi Ueha, Sanshiro Hanada, Toshio Imai, Masako Ito, Kenji Yamamoto, Kouji Matsushima, Akira Yamaguchi, Tadahiro Iimura
    JOURNAL OF CELL SCIENCE 126 4 1032 - 1045 2013年02月 [査読有り][通常論文]
     
    Chemokines have recently been reported to be involved in pathological bone destruction. However, the physiological roles of chemokines in bone metabolism in vivo have not been well documented. We analyzed the bone phenotypes in Cx3cr1-deficient mice. The mice exhibited slight but significant increases in trabecular and cortical thickness, reduced numbers of osteoclasts and increased rates of osteoid formation. Although the morphometric parameters showed marginal differences, the Cx3cr1-deficient bones showed an elevated expression of Osterix/SP7, which encodes an essential transcriptional factor for osteoblasts, whereas the gene Osteocalcin/Bglap, which encodes a late marker, was downregulated. The levels of transcripts for various osteoclastic markers, such as receptor activator of NF-kappa B (RANK)/TNFRSF11A, receptor activator of NF-kB ligand (RANKL)/TNFSF11, tartrate-resistant acid phosphatase 5b (TRAP5B)/ACP5B, Cathepsin K(CTSK), MMP3 and MMP13, were significantly decreased in the Cx3cr1-deficient bones. Cultured Cx3cr1-deficient osteoblastic cells showed inverse temporal patterns of osteoblastic marker expression and reduced calcium deposition. Furthermore, in vitro studies and immunofluorescence staining against CX3CR1 and CX3CL1 suggested a role for the CX3CR1-CX3CL1 axis in an early stage of osteoblast differentiation, possibly through their trans and cis interactions. Cultured Cx3cr1-deficient pre-osteoclasts showed impaired differentiation, mainly due to a deficiency of the CD115(+)CD11b(10) osteoclastogenic population ofmyeloid-lineage precursors. The treatment of bone-marrow-derived osteoclastic cultures with recombinant CX3CL1 at different time points suggested that the CX3CR1-CX3CL1 axis favors the maintenance of osteoclastic precursors, but not differentiated osteoclasts. These observations uncovered novel roles of the CX3CR1-CX3CL1 axis in the differentiation of both osteoblasts and osteoclasts.
  • Yuji Makinoa, Kazuo Kanekob, Akira Yamaguchia, Tadahiro Iimura
    Journal of Oral Biosciences 55 4 175 - 179 2013年 [査読有り][通常論文]
     
    Skeletal patterningistightlylinkedtoembryonicmorphogenesis. Accumulatedevidenceongenotype- phenotype analysesinmodelanimalsandhumanhasuncoveredmolecularsignalsthatparticipate in skeletalsize,shape,andspatialorganization. Embryonicmorphogenesisendowsmorphologicalin-formation togroupsofskeletalprecursors.Accordingly, someofthecongenitalskeletaldisordersare manifested asdefectsinembryogenesispriortoskeletaltissuedifferentiationandpathologicallyca tegorizedasdysostosis.Spondylocostaldysostosis(SCDO) andspondylothoracicdysostosis(STDO) are skeletaldisordersthatarehighlyspecific totheaxialskeleton,vertebrae,andribs,whoseembryonicorigin isthesegmentedmesodermalstructurecalledsomite. Thegenesresponsibleforthesediseases haverecentlybeenidentified andareoperatedduringsomiteformation.Currentinvestigationson organogenesis ofmousemodelsofSCDOandSTDOuncoveredtheexistenceofmorecomplicatedregulatorysteps forthespatiotemporalorganizationoftheaxialskeletonthantheoriginalviewofdirectli nkbetweenmorphogenesisandskeletalpatterning.Molecularandcellular findings inaxialskeleton development areexpectedtocontributetodevelopmoreefficient therapeuticstrategiesagainstcommon medical problems.©2013 Japanese Association for Oral Biology.Published by Elsevier B.V.All rights reserved.
  • 進行性/特発性下顎頭吸収におけるケモカイン受容体異常により生じる骨/軟骨減少に関する研究(Study of Osteo-/Chondropenia Caused by Impaired Chemokine Receptor and for Progressive/Idiopathic Condylar Resorption)
    Maruoka Yutaka, Kanaya Fumihide, Hoshino Akiyoshi, Iimura Tadahiro, Imai Hideki, Otsuka Ryo, Ueha Satoshi, Fujioka Kohki, Katsuragawa Yozo, Shimbo Takuro, Mimori Akio, Yamazaki Tsutomu, Manome Yoshinobu, Moriyama Keiji, Omura Ken, Matsushima Kouji, Yamamoto Kenji
    日本顎変形症学会雑誌 22 補冊 S15 - S22 (NPO)日本顎変形症学会 2012年12月 [査読有り][通常論文]
     
    日本国内の進行性下顎頭吸収(PCR)の179症例を検討した。自覚症状を伴わないPCR患者が多くみられた。患者の一部は咬合不調和のため口腔外科よりも矯正歯科を受診していた。患者の多くを女性が占めた。PCR患者は特発性の若年患者と自己免疫疾患などの合併症がある50代以上の患者の二峰性分布を示した。PCR患者の主訴として顎関節症よりも咬合不調和が多かった。一側性よりも両側性障害が多かった。PCR患者の初診時の診断の多くは顎関節症であり、両疾患の判別の困難さが示唆された。PCRの治療は顎関節症に対するものと同様であった。単純な顎関節症、顎変形や咬合異常と診断され、適切な治療を受けていないPCR患者の存在が示唆された。
  • Takashi Watanabe, Yoshihiro Tamamura, Akiyoshi Hoshino, Yuji Makino, Hiroshi Kamioka, Teruo Amagasa, Akira Yamaguchi, Tadahiro Iimura
    BONE 51 3 447 - 458 2012年09月 [査読有り][通常論文]
     
    Confocal immunofluorescence tiling imaging revealed the spatio-temporal distributions of osterix and sclerostin in femurs from 3-day-old, 2-week-old and 4-week-old rats to be reciprocally exclusive at the tissue level. Further quantitative three-dimensional immuno fluorescence morphometry demonstrated the increasing distribution of sclerostin in the osteocytic lacuno-canalicular system specifically in diaphysis, which paralleled the cooperative participation and depletion of osterix and beta-catenin in adjacent periosteum cells. Treating MC3T3-E1 cells with BIO (a GSK3 inhibitor) induced the stabilization of beta-catenin and nuclear translocation of osterix, and negatively regulated osteocalcin/BGLAP and Dmp1. These results collectively demonstrate that the increasing distribution of sclerostin in diaphyseal cortical bone appears to be involved in the attenuation of osterix and beta-catenin in adjacent periosteum cells, thus possibly contributing to osteoblast maturation and reducing the osteoblast formation at this bone site. Our confocal microscopy-based imaging analyses provide a comprehensive and detailed view of the spatio-temporal distribution of sclerostin, beta-catenin and osterix at the tissue to subcellular level in a coherent manner, and uncovered their spatio-temporal cooperation in postnatal bone development, thus providing evidence that they link skeletogenic growth and functional bone development. (C) 2012 Elsevier Inc. All rights reserved.
  • Kohsuke Umehara, Tadahiro Iimura, Kei Sakamoto, Zayar Lin, Shohei Kasugai, Yoshimasa Igarashi, Akira Yamaguchi
    ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY 295 8 1327 - 1335 2012年08月 [査読有り][通常論文]
     
    Several lines of evidence show that transplantation of osteoblastic cells or genetically engineered nonosteogenic cells expressing osteoblast-related genes into bone defects effectively promotes bone regeneration. To extend this possibility, we investigated whether oral mucosal fibroblasts are capable of differentiating into osteoblastic cells by conducting in vitro and in vivo experiments. We investigated the effects of bone morphogenetic protein-2 (BMP-2) on osteoblast differentiation of cultured fibroblasts isolated from canine buccal mucosa. We also transplanted green fluorescence protein (GFP)-expressing fibroblasts with gelatin/BMP-2 complexes into the subfascial regions of athymic mice, and investigated the localization of GFP-positive cells in the ectopically formed bones. The cultured canine buccal mucosal fibroblasts differentiated into osteoblastic cells by increasing their alkaline phosphatase (ALP) activity and Osteocalcin, Runx2, and Osterix mRNA expression levels in response to BMP-2. Transplantation experiments of GFP-expressing oral mucosal fibroblasts with gelatin/BMP-2 complexes revealed that 17.1% of the GFP-positive fibroblasts differentiated into ALP-positive cells, and these cells accounted for 6.2% of total ALP-positive cells in the ectopically formed bone. This study suggests that oral mucosal fibroblasts can differentiate into osteogenic cells in response to BMP-2. Thus, these cells are potential candidates for cell-mediated bone regeneration therapy in dentistry. Anat Rec, 2012. (C) 2012 Wiley Periodicals, Inc.
  • Erika Oue, Ji-Won Lee, Kei Sakamoto, Tadahiro Iimura, Kazuhiro Aoki, Kou Kayamori, Yasuyuki Michi, Masashi Yamashiro, Kiyoshi Harada, Teruo Amagasa, Akira Yamaguchi
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 424 3 456 - 461 2012年08月 [査読有り][通常論文]
     
    To explore the mechanism of bone destruction associated with oral cancer, we identified factors that stimulate osteoclastic bone resorption in oral squamous cell carcinoma. Two clonal cell lines, HSC3-C13 and HSC3-C17, were isolated from the maternal oral cancer cell line, HSC3. The conditioned medium from HSC3-C13 cells showed the highest induction of Rankl expression in the mouse stromal cell lines ST2 and UAMS-32 as compared to that in maternal HSC3 cells and HSC3-C17 cells, which showed similar activity. The conditioned medium from HSC3-C13 cells significantly increased the number of osteoclasts in a co-culture with mouse bone marrow cells and UAMS-32 cells. Xenograft tumors generated from these clonal cell lines into the periosteal region of the parietal bone in athymic mice showed that HSC3-C13 cells caused extensive bone destruction and a significant increase in osteoclast numbers as compared to HSC3-C17 cells. Gene expression was compared between HSC3-C13 and HSC3-C17 cells by using microarray analysis, which showed that CXCL2 gene was highly expressed in HSC3-C13 cells as compared to HSC3-C17 cells. Immunohistochemical staining revealed the localization of CXCL2 in human oral squamous cell carcinomas. The increase in osteoclast numbers induced by the HSC3-C13-conditioned medium was dose-dependently inhibited by addition of anti-human CXCL2-neutralizing antibody in a co-culture system. Recombinant CXCL2 increased the expression of Rankl in UAMS-32 cells. These results indicate that CXCL2 is involved in bone destruction induced by oral cancer. This is the first report showing the role of CXCL2 in cancer-associated bone destruction. (C) 2012 Elsevier Inc. All rights reserved.
  • Tadahiro Iimura, Ayako Nakane, Mayu Sugiyama, Hiroki Sato, Yuji Makino, Takashi Watanabe, Yuzo Takagi, Rika Numano, Akira Yamaguchi
    JOURNAL OF BONE AND MINERAL METABOLISM 30 3 254 - 269 2012年05月 [査読有り][通常論文]
     
    Biological phenomena that exhibit periodic activity are often referred as biorhythms or biological clocks. Among these, circadian rhythms, cyclic patterns reflecting a 24-h cycle, are the most obvious in many physiological activities including bone growth and metabolism. In the late 1990s, several clock genes were isolated and their primary structures and functions were identified. The feedback loop model of transcriptional factors was proposed to work as a circadian core oscillator not only in the suprachiasmatic nuclei of the anterior hypothalamus, which is recognized as the mammalian central clock, but also in various peripheral tissues including cartilage and bone. Looking back to embryonic development, the fundamental architecture of skeletal patterning is regulated by ultradian clocks that are defined as biorhythms that cycle more than once every 24 h. As post-genomic approaches, transcriptome analysis by micro-array and bioimaging assays to detect luminescent and fluorescent signals have been exploited to uncover a more comprehensive set of genes and spatio-temporal regulation of the clockwork machinery in animal models. In this review paper, we provide an overview of topics related to these molecular clocks in skeletal biology and medicine, and discuss how fluorescence imaging approaches can contribute to widening our views of this realm of biomedical science.
  • Ryo Aizawa, Atsushi Yamada, Dai Suzuki, Tadahiro Iimura, Hidetoshi Kassai, Takeshi Harada, Masayuki Tsukasaki, Gou Yamamoto, Tetsuhiko Tachikawa, Kazuki Nakao, Matsuo Yamamoto, Akira Yamaguchi, Atsu Aiba, Ryutaro Kamijo
    MECHANISMS OF DEVELOPMENT 129 1-4 38 - 50 2012年03月 [査読有り][通常論文]
     
    Cdc42, a member of the Rho subfamily of small GTPases, is known to be a regulator of multiple cellular functions, including cytoskeletal organization, cell migration, proliferation, and apoptosis. However, its tissue-specific roles, especially in mammalian limb development, remain unclear. To investigate the physiological function of Cdc42 during limb development, we generated limb bud mesenchyme-specific inactivated Cdc42 (Cdc42(fl/fl); Prx1-Cre) mice. Cdc42(fl/fl); Prx1-Cre mice demonstrated short limbs and body, abnormal calcification of the cranium, cleft palate, disruption of the xiphoid process, and syndactyly. Severe defects were also found in long bone growth plate cartilage, characterized by loss of columnar organization of chondrocytes, and thickening and massive accumulation of hypertrophic chondrocytes, resulting in delayed endochondral bone formation associated with reduced bone growth. In situ hybridization analysis revealed that expressions of Col10 and Mmp13 were reduced in non-resorbed hypertrophic cartilage, indicating that deletion of Cdc42 inhibited their terminal differentiation. Syndactyly in Cdc42(fl/fl); Prx1-Cre mice was caused by fusion of metacarpals and a failure of interdigital programmed cell death (ID-PCD). Whole mount in situ hybridization analysis of limb buds showed that the expression patterns of Sox9 were ectopic, while those of Bmp2, Msx1, and Msx2, known to promote apoptosis in the interdigital mesenchyme, were down-regulated. These results demonstrate that Cdc42 is essential for chondrogenesis and ID-PCD during limb development. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
  • Akiko Himeno-Ando, Yuichi Izumi, Akira Yamaguchi, Tadahiro Iimura
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 417 2 765 - 770 2012年01月 [査読有り][通常論文]
     
    The structural features of osteocytes and their cellular process network are thought to allow for mechanotransduction from the bone tissue to these cells. This study applied three-dimensional fluorescence microscopy to fixed and decalcified bone specimens to quantitatively compare the osteocytes and their networks between mouse parietal bone and tibia that are physiologically enforced by distinct mechanical loads. The subsequent morphometric analysis by the surface rendering of osteocyte cell bodies revealed the tibia to have relatively enriched cytoplasm in the osteocyte cell body in comparison to the parietal bone. Furthermore, quantitative tracing of the cellular processes in silico demonstrated that the numbers of the cellular processes and their bifurcation points per osteocyte in the tibia were significantly higher than those in the parietal bone. Though the total length of the processes per osteocyte in the tibia was two times longer, its total surface area and total volume were smaller than those in the parietal bone, due to its thinner diameter. These architectural differences in the osteocytes and their networks are thus implicated in the adaptation to physiologically different loading, and may also induce distinct mechanosensitivities. (C) 2011 Elsevier Inc. All rights reserved.
  • Lei Cao, Takeshi Moriishi, Toshihiro Miyazaki, Tadahiro Iimura, Miwako Hamagaki, Ayako Nakane, Yoshihiro Tamamura, Toshihisa Komori, Akira Yamaguchi
    JOURNAL OF BONE AND MINERAL METABOLISM 29 6 662 - 670 2011年11月 [査読有り][通常論文]
     
    Osteocytes are embedded in the bone matrix, and they communicate with adjacent osteocytes, osteoblasts, and osteoclasts through the osteocyte lacunocanalicular system. Osteocytes are believed to be essential for the maintenance of bone homeostasis because they regulate mechanical sensing and mineral metabolism in mammalian bones; however, osteocyte morphology in other vertebrates has not been well documented. We conducted a comparative study on the morphology of osteocytes and the lacunocanalicular system of the following vertebrates: two teleost fishes [medaka (Oryzias latipes), and zebrafish (Danio rerio)], three amphibians [African clawed frog (Xenopus laevis), black-spotted pond frog (Rana nigromaculata), and Japanese fire-bellied newt (Cynops pyrrhogaster)], two reptiles [four-toed tortoise (Testudo horsfieldii) and green iguana (Iguana iguana)], and two mammals (laboratory mouse C57BL6 and human). The distribution of the osteocyte lacunocanalicular system in all these animals was investigated using the modified silver staining and the fluorescein-conjugated phalloidin staining methods. Bones of medaka had few osteocytes (acellular bone). Bones of zebrafish contained osteocytes (cellular bone) but had a poorly developed osteocyte lacunocanalicular system. Bones of Xenopus laevis, a freshwater species, and of other amphibians, reptiles, and mammals contained numerous osteocytes and a well-developed lacunocanalicular system. The present study indicates that development of the osteocyte lacunocanalicular system differs between teleost fishes and land vertebrates, but this pattern is not directly related to aquatic habitat.
  • イヌの口腔粘膜線維芽細胞とrhBMP2を利用した骨再生療法の可能性の検討
    梅原 康佑, 五十嵐 順正, 飯村 忠浩, 山口 朗
    口腔病学会雑誌 78 1 46 - 46 口腔病学会 2011年03月 [査読無し][通常論文]
  • Tadahiro Iimura, Mayu Sugiyama, Takashi Watanabe, Ayako Nakane, Yuji Makino, Akira Yamaguchi
    Journal of Oral Biosciences 53 2 97 - 108 2011年 [査読有り][通常論文]
     
    Skeletal development and bone homeostasis are dynamic but coordinated cellular process that involves proliferation, migration and differentiation. Molecular biology and genome science promoted this realm of biomedical science by elucidating cell lineages and essential molecules and their interactions. Fluorescence live imaging has made it possible to quantitatively analyze multi-cellular processes in 4 dimensions, thus providing coherent understanding of distinct levels of description from molecular levels to the tissue, organ and organism. Application of this approach has given further insight into and comprehension of the dynamic process of, not a mere description of the molecular hierarchy, skeletal biology. In this review paper, how fluorescent imaging has shed new light on the skeletal biology will be discussed. We introduce several current topics in the application of fluorescent imaging on skeletal patterning, morphometry of bone cells and cellular behavior in bone marrow.
  • Akiyoshi Hoshino, Tadahiro Iimura, Satoshi Ueha, Sanshiro Hanada, Yutaka Maruoka, Mitsuori Mayahara, Keiko Suzuki, Toshio Imai, Masako Ito, Yoshinobu Manome, Masato Yasuhara, Takaaki Kirino, Akira Yamaguchi, Kouji Matsushima, Kenji Yamamoto
    JOURNAL OF BIOLOGICAL CHEMISTRY 285 37 28826 - 28837 2010年09月 [査読有り][通常論文]
     
    Chemokines are characterized by the homing activity of leukocytes to targeted inflammation sites. Recent research indicates that chemokines play more divergent roles in various phases of pathogenesis as well as immune reactions. The chemokine receptor, CCR1, and its ligands are thought to be involved in inflammatory bone destruction, but their physiological roles in the bone metabolism in vivo have not yet been elucidated. In the present study, we investigated the roles of CCR1 in bone metabolism using CCR1-deficient mice. Ccr1(-/-) mice have fewer and thinner trabecular bones and low mineral bone density in cancellous bones. The lack of CCR1 affects the differentiation and function of osteoblasts. Runx2, Atf4, Osteopontin, and Osteonectin were significantly up-regulated in Ccr1(-/-) mice despite sustained expression of Osterix and reduced expression of Osteocalcin, suggesting a lower potential for differentiation into mature osteoblasts. In addition, mineralized nodule formation was markedly disrupted in cultured osteoblastic cells isolated from Ccr1(-/-) mice. Osteoclastogenesis induced from cultured Ccr1(-/-) bone marrow cells yielded fewer and smaller osteoclasts due to the abrogated cell-fusion. Ccr1(-/-) osteoclasts exerted no osteolytic activity concomitant with reduced expressions of Rank and its downstream targets, implying that the defective osteoclastogenesis is involved in the bone phenotype in Ccr1(-/-) mice. The co-culture of wild-type osteoclast precursors with Ccr1(-/-) osteoblasts failed to facilitate osteoclastogenesis. This finding is most likely due to a reduction in Rankl expression. These observations suggest that the axis of CCR1 and its ligands are likely to be involved in crosstalk between osteoclasts and osteoblasts by modulating the RANK-RANKL-mediated interaction.
  • Kou Kayamori, Kei Sakamoto, Tomoki Nakashima, Hiroshi Takayanagi, Kei-ichi Morita, Ken Omura, Su Tien Nguyen, Yoshio Miki, Tadahiro Iimura, Akiko Himeno, Takumi Akashi, Hisafumi Yamada-Okabe, Etsuro Ogata, Akira Yamaguchi
    AMERICAN JOURNAL OF PATHOLOGY 176 2 968 - 980 2010年02月 [査読有り][通常論文]
     
    We investigated the roles of interleukin-6 (IL-6) and parathyroid hormone-related peptide (PTHrP) in oral squamous cell carcinoma (OSCC)-induced osteoclast formation. Microarray analyses performed on 43 human OSCC specimens revealed that many of the specimens overexpressed PTHrP mRNA, but a few overexpressed IL-6 mRNA. immunohistochemical analysis revealed that IL-6 was expressed not only in cancer cells but also in fibroblasts and osteoclasts at the tumor-bone interface. Many of the IL-6-positive cells coexpressed vimentin. Conditioned medium (CM) derived from the culture of oral cancer cell lines (BHY, Ca9-22, HSC3, and HO1-u-1) stimulated Rankl expression in stromal cells and osteoclast formation. Antibodies against both human PTHrP and mouse IL-6 receptor suppressed Rankl in ST2 cells and osteoclast formation induced by CM from BHY and Ca9-22, although the inhibitory effects of IL6 antibody were greater than those of PTHrP antibody. CM derived from all of the OSCC cell lines effectively induced IL-6 expression in stromal cells, and the induction was partially blocked by anti-PTHrP antibody. Xenografts of HSC3 cells onto the periosteal region of the parietal bone in athymic mice presented histology and expression profiles of RANKL and IL-6 similar to those observed in bone-invasive human OSCC specimens. These results indicate that OSCC provides a suitable microenvironment for osteoclast formation not only by producing IL-6 and PTHrP but also by stimulating stromal cells to synthesize IL-6. (Am J Pathol 2010, 176:968-980; DOI: 10.2353/ajpath.2010.090299)
  • Kou Kayamori, Kei Sakamoto, Tomoki Nakashima, Hiroshi Takayanagi, Kei-Ichi Morita, Ken Omura, Su Tien Nguyen, Yoshio Miki, Tadahiro Iimura, Akiko Himeno, Takumi Akashi, Hisafumi Yamada-Okabe, Etsuro Ogata, Akira Yamaguchi
    American Journal of Pathology 176 2 968 - 980 2010年 [査読有り][通常論文]
     
    We investigated the roles of interleukin-6 (IL-6) and parathyroid hormone-related peptide (PTHrP) in oral squamous cell carcinoma (OSCC)-induced osteoclast formation. Microarray analyses performed on 43 human OSCC specimens revealed that many of the specimens overexpressed PTHrP mRNA, but a few overexpressed IL-6 mRNA. Immunohistochemical analysis revealed that IL-6 was expressed not only in cancer cells but also in fibroblasts and osteoclasts at the tumor-bone interface. Many of the IL-6-positive cells coexpressed vimentin. Conditioned medium (CM) derived from the culture of oral cancer cell lines (BHY, Ca9-22, HSC3, and HO1-u-1) stimulated Rankl expression in stromal cells and osteoclast formation. Antibodies against both human PTHrP and mouse IL-6 receptor suppressed Rankl in ST2 cells and osteoclast formation induced by CM from BHY and Ca9-22, although the inhibitory effects of IL6 antibody were greater than those of PTHrP antibody. CM derived from all of the OSCC cell lines effectively induced IL-6 expression in stromal cells, and the induction was partially blocked by anti-PTHrP antibody. Xenografts of HSC3 cells onto the periosteal region of the parietal bone in athymic mice presented histology and expression profiles of RANKL and IL-6 similar to those observed in bone-invasive human OSCC specimens. These results indicate that OSCC provides a suitable microenvironment for osteoclast formation not only by producing IL-6 and PTHrP but also by stimulating stromal cells to synthesize IL-6. Copyright © American Society for Investigative Pathology.
  • Tadahiro Iimura, Akiko Himeno, Ayako Nakane, Akira Yamaguchi
    Journal of Oral Biosciences 52 2 155 - 163 2010年 [査読有り][通常論文]
     
    A set of Hox genes expressed during the embryonic process presents a crucial system to set up the body plan in animal phyla. Current systematic approaches, such as bio-imaging, epigenetic regulation and phylogenetic genome comparison, illuminated new comprehensive insights into Hox genes as an evolu-tionary constraint of the vertebrate body plan, which provides a novel counter-view to give further insights into the evolution and development of the craniofacial and dental systems as non-Hox systems.
  • Mayu Sugiyama, Asako Sakaue-Sawano, Tadahiro Iimura, Kiyoko Fukami, Tetsuya Kitaguchi, Koichi Kawakami, Hitoshi Okamoto, Shin-ichi Higashijima, Atsushi Miyawaki
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 106 49 20812 - 20817 2009年12月 [査読有り][通常論文]
     
    By exploiting the cell-cycle-dependent proteolysis of two ubiquitination oscillators, human Cdt1 and geminin, which are the direct substrates of SCF(Skp2) and APC(Cdh1) complexes, respectively, Fucci technique labels mammalian cell nuclei in G(1) and S/G(2)/M phases with different colors. Transgenic mice expressing these G(1) and S/G2/M markers offer a powerful means to investigate the coordination of the cell cycle with morphogenetic processes. We attempted to introduce these markers into zebrafish embryos to take advantage of their favorable optical properties. However, although the fundamental mechanisms for cell-cycle control appear to be well conserved among species, the G(1) marker based on the SCF(Skp2)-mediated degradation of human Cdt1 did not work in fish cells, probably because the marker was not ubiquitinated properly by a fish E3 ligase complex. We describe here the generation of a Fucci derivative using zebrafish homologs of Cdt1 and geminin, which provides sweeping views of cell proliferation in whole fish embryos. Remarkably, we discovered two anterior-to-posterior waves of cell-cycle transitions, G(1)/S and M/G(1), in the differentiating notochord. Our study demonstrates the effectiveness of using the Cul4(Ddb1)-mediated Cdt1 degradation pathway common to all metazoans for the development of a G(1) marker that works in the nonmammalian animal model.
  • Tadahiro Iimura, Nicolas Denans, Olivier Pourquie
    HOX GENES 88 201 - + 2009年 [査読有り][通常論文]
     
    The vertebrate spine exhibits two striking characteristics. The first one is the periodic arrangement of its elements-the vertebrae-along the anteroposterior axis. This segmented organization is the result of somitogenesis, which takes place during organogenesis. The segmentation machinery involves a molecular oscillator-the segmentation clock-which delivers a periodic signal controlling somite production. During embryonic axis elongation, this signal is displaced posteriorly by a system of traveling signaling gradients-the wavefront-which depends on the Wnt, FGF, and retinoic acid pathways. The other characteristic feature of the spine is the subdivision of groups of vertebrae into anatomical domains, such as the cervical, thoracic, lumbar, sacral, and caudal regions. This axial regionalization is controlled by a set of transcription factors called Hox genes. Hox genes exhibit nested expression domains in the somites which reflect their linear arrangement along the chromosomes-a property termed colinearity. The colinear disposition of Hox genes expression domains provides a blueprint for the regionalization of the future vertebral territories of the spine. In amniotes, Hox genes are activated in the somite precursors of the epiblast in a temporal colinear sequence and they were proposed to control their progressive ingression into the nascent paraxial mesoderm. Consequently, the positioning of the expression domains of Hox genes along the anteroposterior axis is largely controlled by the timing of Hox activation during gastrulation. Positioning of the somitic Hox domains is subsequently refined through a crosstalk with the segmentation machinery in the presomitic mesoderm. In this review, we focus on our current understanding of the embryonic mechanisms that establish vertebral identities during vertebrate development.
  • Miguel Maroto, Tadahiro Iimura, J. Kim Dale, Yasumasa Bessho
    SOMITOGENESIS 638 124 - 139 2008年 [査読有り][通常論文]
     
    The most obvious manifestation of the existence of a segmented, or metameric, body plan in vertebrate embryos is seen during the formation of the somites. Semites are transient embryonic structures formed in a progressive manner from a nonsegmented mesoderm in a highly regulated process called somitogenesis. As development proceeds different compartments are formed within each somite and these progressively follow a variety of differentiation programs to form segmented organs, such as the different bones that make the axial skeleton, body skeletal muscles and part of the dermis. Transcription factors from the basic helix-loop-helix (bHLH) protein family have been described to be implicated in each of the processes involved in somite formation. bHLH proteins are a family of transcription factors characterized by the presence of a DNA binding domain and a dimerization motif chat consists of a basic region adjacent to an amphipathic helix, a loop and a second amphipathic helix. In this chapter we will review a number of bHLH proteins known to play a role in somitogenesis.
  • Tadahiro Iimura, Olivier Pourquie
    AVIAN EMBRYOLOGY, 2ND EDITION 87 257 - + 2008年 [査読有り][通常論文]
     
    The chick embryo has been a leading model in embryological studies, including somitogenesis, because of its easy accessibility for manipulation during most of its development. The recent development of gain- and loss-of-function strategies of specific genes by electroporation has made the chick embryo an even more attractive model for embryological studies. In vitro electroporation, combined with whole chick embryo culture techniques, provides a wide range of possible approaches to study early stages of chick embryogenesis. We will describe in vitro electroporation techniques that are useful to study the development of somites (and any other derivative of the primitive streak and epiblast), and discuss potential applications of these methods.
  • Tadahiro Iimura, Olivier Pourquie
    DEVELOPMENT GROWTH & DIFFERENTIATION 49 4 265 - 275 2007年05月 [査読有り][通常論文]
     
    Vertebrae display distinct morphological features at different levels of the body axis. Links between collinear Hox gene activation and the progressive mode of body axis elongation have provided a fascinating blueprint of the mechanisms for establishing these morphological identities. In this review, we first discuss the regulation and possible role of collinear Hox gene activation during body formation and then highlight the direct role of Hox genes in controlling cellular movements during gastrulation, therefore contributing to body formation. Additional related research aspects, such as imaging of chromatin regulation, roles of micro RNAs and evolutional findings are also discussed.
  • Tadahiro Limura, Xuesong Yang, Cornelis J. Weijer, Olivier Pourquie
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 104 8 2744 - 2749 2007年02月 [査読有り][通常論文]
     
    The skeletal muscles and axial skeleton of vertebrates derive from the embryonic paraxial mesoderm. In amniotes, paraxial mesoderm is formed bilaterally to the nerve cord as a result of primitive streak and tail-bud regression during body axis formation. In chick and mouse embryos, paraxial mesoderm was proposed to derive from a population of resident cells located in the regressing primitive streak and tail bud. in contrast, in lower vertebrates, paraxial mesoderm is formed as a result of the continuation of ingression movements of gastrulation. Here, we reinvestigate paraxial mesoderm formation in the chicken embryo and demonstrate that these two modes are concomitantly at work to set up the paraxial mesoderm. Although the medial part of somites derives from stem cells resident in the primitive streak/tail bud,the lateral part derives from continuous ingression of epiblastic material. Our fate mapping further shows that the paraxial mesoderm territory in the epiblast is regionalized along the anteroposterior axis as in lower vertebrates. These observations suggest that the mechanisms responsible for paraxial mesoderm formation are largely conserved across vertebrates.
  • Hox遺伝子群による中胚葉形成タイミングの制御 脊椎動物のボディフォーメーションにおける時間と空間の新しい連携機構
    飯村 忠浩
    細胞工学 25 11 1294 - 1299 (株)学研メディカル秀潤社 2006年10月 [査読無し][通常論文]
  • Tadahiro Iimura, Olivier Pourquie
    NATURE 442 7102 568 - 571 2006年08月 [査読有り][通常論文]
     
    The vertebral column exhibits segmentation and regionalization along the antero-posterior axis. During embryogenesis, the rhythmic production of the precursors of the vertebrae, the somites, imposes a segmented aspect to the spine, whereas the spine's regional differentiation is controlled by Hox genes(1,2). Here we show that in the paraxial mesoderm, Hoxb genes are first activated in a temporal collinear fashion in precursors located in the epiblast lateral to the primitive streak. Our data suggest that collinear activation of Hoxb genes regulates the flux of cells from the epiblast to the streak and thus directly controls the establishment of the genes' characteristic nested expression domains in the somites. This suggests that establishment of the spatial co-linearity in the embryo is directly controlled by the Hox genes themselves.
  • 飯村 忠浩
    生体の科学 55 5 458 - 459 (公財)金原一郎記念医学医療振興財団 2004年10月 [査読無し][通常論文]
  • 21世紀の歯科医学・医療 歯科医療からみた再生医学 歯・歯周組織の再生医療 頭部神経堤細胞は,頭蓋顔面領域における胚性幹細胞である
    江藤 一洋, 飯村 忠浩
    日本歯科医学会誌 22 92 - 95 日本歯科医学会 2003年03月 [査読無し][通常論文]
  • M Goseki-Sone, A Yamada, R Hamatani, L Mizoi, T Iimura, Ezawa, I
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 299 3 395 - 399 2002年12月 [査読有り][通常論文]
     
    Alkaline phosphatases (ALPs) are glycosylated, membrane-bound enzymes that hydrolyze various monophosphate esters at an optimum high pH and are present in nearly all living organisms. In Escherichia coli, extracellular phosphate (Pi) limitation induces the ALP gene, indicating a role of extracellular Pi in ALP gene regulation. However, little is known about similar mechanisms in mammalian cells. Previously, we reported that Pi starvation increased the tissue-nonspecific ALP (TNSALP) activity and regulated its expression in the mouse stromal cell line ST2, derived from mouse bone marrow. In the present study, we further examined the effects of Pi starvation on the mechanism of TNSALP induction. The specific activity of TNSALP increased markedly after treatment by Pi starvation for 5 days and RT-PCR analysis revealed that the mRNA of the bone morphogenetic protein-4 (BMP-4) gene was highly stimulated. The combination of Pi depletion and mouse BMP-4 receptor IA/Fc chimera down-regulated the TNSALP activity. These results indicated that Pi depletion stimulates the TNSALP activity for the Pi supplementation, and that this system may involve the signaling pathway of the BMP-4 gene at the transcription level. (C) 2002 Elsevier Science (USA). All rights reserved.
  • K Kubota, S Iseki, S Kuroda, S Oida, T Iimura, WR Duarte, K Ohya, Ishikawa, I, S Kasugai
    BONE 31 4 465 - 471 2002年10月 [査読有り][通常論文]
     
    Bone morphogenetic protein family members (BMPs) are essential signaling molecules during limb development and, in this process, fibroblast growth factor family members (FGFs) cooperate with BMPs. FGFs also exert anabolic effects in bone when systemically or locally applied. Thus, it is likely that the cooperation with FGFs also occurs in BMP-induced ectopic bone formation and that the exogenous FGF application would promote this bone formation. In the present study. after subcutaneously implanting recombinant human BMP-2 (rhBMP-2) in rats, we examined the expression of FGF-4 and FGF receptors (FGFRs) mRNAs and the effect of exogenous recombinant human FGF-4 (rhFGF-4) on bone formation. Three days after implantation, the pellets containing rhBMP-2 were surrounded by fibroblastic mesenchymal cells; on day 7, cartilage tissue appeared; on day, 10, hypertrophic chondrocytes and a small amount of mineralized tissue were observed; and, on day 14, the amount of mineralized tissue increased. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that FGF-4 expression appeared at early stages (days 3 and 7) and its expression decreased at later stages (days 10, 14, and 21), whereas FGFRs were expressed continuously. In situ hybridization revealed that, on days 3 and 7, FGF-4, and FGFR subtypes I and 2 (FGFR-1 and FGFR-2) were expressed in mesenchymal cells and chondrocytes, and in the area of alkaline phosphatase (ALP) expression. On day 10, FGF-4 was not detected, whereas the expression of FGFR-1 and FGFR-2 was detectable in the area of alkaline phosphatase (ALP) expression. Injection of rhFGF-4 on days 2, 3, and 4 enhanced the mineralized tissue formation induced by rhBMP-2; however, neither rhFGF-4 treatment on days 6, 7, and 8 nor rhFGF-4 treatment on days 9, 10, and 11 influenced the amount of rhBMP-2-induced mineralization. Our results indicate that FGF-4 and FGFR signals play important roles during rhBMP-2-induced bone formation. We further suggest that the combination of rhBMP-2 and rhFGF-4 would be useful for bone augmentation.
  • 頭蓋顔面骨格の形の分化とパラドックス 頭部神経堤細胞は将来の骨の形を記憶しているのか?
    飯村 忠浩
    The Quintessence 21 10 2219 - 2219 クインテッセンス出版(株) 2002年10月 [査読無し][通常論文]
  • 時を刻む遺伝子と脊椎動物の発生 時間遺伝子と頭蓋顔面の進化
    飯村 忠浩
    The Quintessence 21 8 1779 - 1779 クインテッセンス出版(株) 2002年08月 [査読無し][通常論文]
  • A Yamada, Y Maruoka, K Asahi, T Iimura, S Oida, Ezawa, I, M Goseki-Sone
    JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY 48 3 238 - 241 2002年06月 [査読有り][通常論文]
     
    Swimming is a non-weight-bearing exercise. Therefore it has the advantage of maintaining skeletal integrity in aged persons with weakened skeletal structures. Unlike other weight-bearing aerobic exercises, however, it does not appear to exert sufficient stimulus on bone-remodeling activities because the local load-bearing on bone tissues is mild. The purpose of this study was to investigate the effect of swimming on bone remodeling, especially with the use of implanted pellets containing bone morphogenetic protein (BMP) and demineralized bone matrix during the initial stages of the differentiation of mesenchymal cells to cartilage cells. Six-week-old female rats were divided into the swimming group and a control, nonswimming group. Test animals were forced to swim in a water bath for 30 min daily for 2 wk. After the swimming protocol, pellets were implanted and harvested. Messenger RNA isolated from pellets was quantified by means of a reverse transcription-polymerase chain reaction. The expression of RNAs for bone sialoprotein and BMP-6 in pellets from the swimming group was apparently enhanced at 7 d after implantation. These results suggested that systemic hormonal and/or metabolic changes that promote cartilage formation might have occurred after swimming because the effect was observed after the swimming protocol had ended and the pellets were implanted at a non-weight-bearing site.
  • 時を刻む遺伝子と脊椎動物の発生 幹細胞と時間遺伝子の関係
    飯村 忠浩
    The Quintessence 21 6 1368 - 1368 クインテッセンス出版(株) 2002年06月 [査読無し][通常論文]
  • 時を刻む遺伝子と脊椎動物の発生 頭や顔の発生と時計遺伝子の関係
    飯村 忠浩
    The Quintessence 21 4 907 - 907 クインテッセンス出版(株) 2002年04月 [査読無し][通常論文]
  • C Jouve, T Iimura, O Pourquie
    DEVELOPMENT 129 5 1107 - 1117 2002年03月 [査読有り][通常論文]
     
    Vertebrate somitogenesis is associated with a molecular oscillator, the segmentation clock, which is defined by the periodic expression of genes related to the Notch pathway such as hairy1 and hairy2 or lunatic fringe (referred to as the cyclic genes) in the presomitic mesoderm (PSM). Whereas earlier studies describing the periodic expression of these genes have essentially focussed on later stages of somitogenesis, we have analysed the onset of the dynamic expression of these genes during chick gastrulation until formation of the first somite. We observed that the onset of the dynamic expression of the cyclic genes in chick correlated with ingression of the paraxial mesoderm territory from the epiblast into the primitive streak. Production of the paraxial mesoderm from the primitive streak is a continuous process starting with head mesoderm formation, while the streak is still extending rostrally, followed by somitic mesoderm production when the streak begins its regression. We show that head mesoderm formation is associated with only two pulses of cyclic gene expression. Because such pulses are associated with segment production at the body level, it suggests the existence of, at most, two segments in the head mesoderm. This is in marked contrast to classical models of head segmentation that propose the existence of more than five segments. Furthermore, oscillations of the cyclic genes are seen in the rostral primitive streak, which contains stem cells from which the entire paraxial mesoderm originates. This indicates that the number of oscillations experienced by somitic cells is correlated with their position along the AP axis.
  • 時を刻む遺伝子と脊椎動物の発生 骨のかたちと発生における時間の関係
    飯村 忠浩
    The Quintessence 21 2 451 - 451 クインテッセンス出版(株) 2002年02月 [査読無し][通常論文]
  • 頭蓋顔面骨格の発生と線維芽細胞増殖因子(FGF) 頭蓋骨癒合症と骨芽細胞の分化メカニズム
    飯村 忠浩
    The Quintessence 20 12 2603 - 2603 クインテッセンス出版(株) 2001年12月 [査読無し][通常論文]
  • 頭蓋顔面骨格の発生と線維芽細胞増殖因子(FGF) FGF2は頭部神経堤細胞の骨格系細胞への分化を刺激する
    飯村 忠浩
    The Quintessence 20 10 2142 - 2142 クインテッセンス出版(株) 2001年10月 [査読無し][通常論文]
  • FGF-8とBMP-4は上下顎隆起の発生する場所を決めている
    飯村 忠浩
    The Quintessence 20 8 1697 - 1697 クインテッセンス出版(株) 2001年08月 [査読無し][通常論文]
  • Msx-1及びMax-2のダブルノックアウトマウスと歯の発生
    飯村 忠浩
    The Quintessence 20 6 1243 - 1243 クインテッセンス出版(株) 2001年06月 [査読無し][通常論文]
  • Msx-2はエナメル芽細胞の発生に必須の遺伝子である
    飯村 忠浩
    The Quintessence 20 4 176 - 176 クインテッセンス出版(株) 2001年04月 [査読無し][通常論文]
  • 【再生医学の最前線】 歯・顎顔面の発生と再生
    飯村 忠浩, 江藤 一洋
    分子心血管病 2 1 41 - 51 (株)先端医学社 2001年02月 [査読無し][通常論文]
     
    歯周病によって,歯周組織が失われると,歯そのものが健全でも歯を失うことになり,咀嚼や構音等の口腔機能を低下させる.しかしながら,歯周組織治療薬エムドゲインの登場によって,歯周組織を再生修復することが臨床的に可能になった.生物学的方法で口腔機能の改善が可能になったというこの事実は,歯科医療に大きなパラダイムの転換を迫るものになりそうである.エムドゲイン開発の大きなきっかけになったのは,発生の重要なイベントである組織間相互作用,即ち上皮-間葉の相互作用を模倣したことである.歯と顎顔面の発生学の立場から,歯科領域における再生医療の可能性について述べた
  • 歯科医のためのDNA学再入門 メンデルのエンドウ豆から,ポストゲノムまで ヒトの遺伝子とポストゲノム時代の歯科医学
    飯村 忠浩
    The Quintessence 20 2 403 - 412 クインテッセンス出版(株) 2001年02月 [査読無し][通常論文]
  • Msx 1は口蓋裂の責任遺伝子か?
    飯村 忠浩
    The Quintessence 20 2 421 - 421 クインテッセンス出版(株) 2001年02月 [査読無し][通常論文]
  • 【21世紀の歯科医学 再生歯科医学の幕開け】 21世紀の分子歯科医学 幹細胞と再生歯科医学
    飯村 忠浩, 江藤 一洋
    The Quintessence 20 1 85 - 94 クインテッセンス出版(株) 2001年01月 [査読無し][通常論文]
  • メンデルのエンドウ豆から,ポストゲノムまで(その1) 遺伝子,染色体,DNA,そして誰でも持っている遺伝子異常
    飯村 忠浩
    The Quintessence 20 1 207 - 217 クインテッセンス出版(株) 2001年01月 [査読無し][通常論文]
  • 先天的な歯の数の減少と遺伝子変異 歯数の減少は進化か? あるいは遺伝子異常か?
    飯村 忠浩
    The Quintessence 19 12 2531 - 2531 クインテッセンス出版(株) 2000年12月 [査読無し][通常論文]
  • FRONT ATLAS 頭蓋顎顔面の分子発生学 遺伝子DNAは発生をどう説明するのか? 遺伝子・かたちの変化・そして時間
    飯村 忠浩, 江藤 一洋
    The Quintessence 19 12 2353 - 2367 クインテッセンス出版(株) 2000年12月 [査読無し][通常論文]
  • 頭蓋顎顔面の分子発生学 脳神経の発生 脳神経を解きほぐす
    飯村 忠浩, 江藤 一洋
    The Quintessence 19 11 2147 - 2154 クインテッセンス出版(株) 2000年11月 [査読無し][通常論文]
  • アトラス特別講座 頭蓋顎顔面の分子発生学 頭蓋の発生と発生異常
    飯村 忠浩, 江藤 一洋
    The Quintessence 19 10 1933 - 1939 クインテッセンス出版(株) 2000年10月 [査読無し][通常論文]
  • New Bio-science for Dental Field 過剰歯と鎖骨頭蓋異形成症の責任遺伝子(CBFA1) その変異がもたらすもの
    飯村 忠浩
    The Quintessence 19 10 2123 - 2123 クインテッセンス出版(株) 2000年10月 [査読無し][通常論文]
  • 頭蓋顎顔面の分子発生学 歯の発生 歯周組織の発生と再生
    飯村 忠浩, 江藤 一洋
    The Quintessence 19 9 1723 - 1729 クインテッセンス出版(株) 2000年09月 [査読無し][通常論文]
  • ラット初期胚におけるN-Deacetylase/N-Sulfotransferase(NDST)の発現
    池田 美子, 飯村 忠浩, 柳下 正樹
    歯科基礎医学会雑誌 42 5抄録集 408 - 408 (一社)歯科基礎医学会 2000年08月 [査読無し][通常論文]
  • 頭蓋顎顔面の分子発生学 歯の発生 歯胚のシグナル中心 エナメル結節と歯冠形態の形成
    飯村 忠浩, 江藤 一洋
    The Quintessence 19 8 1509 - 1515 クインテッセンス出版(株) 2000年08月 [査読無し][通常論文]
  • 鎖骨頭蓋異形成症と代謝性骨疾患
    飯村 忠浩
    The Quintessence 19 8 1700 - 1700 クインテッセンス出版(株) 2000年08月 [査読無し][通常論文]
  • 頭蓋顎顔面の分子発生学 歯の発生 上皮-間葉相互作用と分子シグナルネットワーク
    飯村 忠浩, 江藤 一洋
    The Quintessence 19 7 1315 - 1322 クインテッセンス出版(株) 2000年07月 [査読無し][通常論文]
  • 若年性歯周炎とカテプシンC遺伝子の変異
    飯村 忠浩
    The Quintessence 19 6 1291 - 1291 クインテッセンス出版(株) 2000年06月 [査読無し][通常論文]
  • 頭蓋顎顔面の分子発生学 歯の発生 歯胚の誘導
    飯村 忠浩, 江藤 一洋
    The Quintessence 19 6 1097 - 1104 クインテッセンス出版(株) 2000年06月 [査読無し][通常論文]
  • 医学用語解説 Hox遺伝子群
    飯村 忠浩
    炎症と免疫 8 4 468 - 471 (株)先端医学社 2000年06月 [査読無し][通常論文]
  • 頭蓋顎顔面の分子発生学 顎顔面の発生 頭部神経堤細胞は顎顔面の発生の主役である(2)
    飯村 忠浩, 江藤 一洋
    The Quintessence 19 5 875 - 882 クインテッセンス出版(株) 2000年05月 [査読無し][通常論文]
  • 頭蓋顎顔面の分子発生学 顎顔面の発生 頭部神経堤細胞は顎顔面の発生の主役である(1)
    飯村 忠浩, 江藤 一洋
    The Quintessence 19 4 661 - 668 クインテッセンス出版(株) 2000年04月 [査読無し][通常論文]
  • 歯胚の発生位置を決めるメカニズム FGFとBMPの2つのシグナルが歯胚形成領域を決める
    飯村 忠浩
    The Quintessence 19 4 847 - 848 クインテッセンス出版(株) 2000年04月 [査読無し][通常論文]
  • 頭蓋顎顔面の分子発生学 顎顔面の発生 顔面の原基の形態形成
    飯村 忠浩, 江藤 一洋
    The Quintessence 19 3 447 - 453 クインテッセンス出版(株) 2000年03月 [査読無し][通常論文]
  • 頭蓋顎顔面の分子発生学 三胚葉の成立と頭部の誘導 受精卵から頭蓋顎顔面の原基のできるまで
    飯村 忠浩, 江藤 一洋
    The Quintessence 19 2 233 - 240 クインテッセンス出版(株) 2000年02月 [査読無し][通常論文]
  • 胚発生における歯種の決定メカニズム 切歯か臼歯かは胚発生過程の顎のなかで決定される
    飯村 忠浩
    The Quintessence 19 2 413 - 414 クインテッセンス出版(株) 2000年02月 [査読無し][通常論文]
  • 頭蓋顎顔面の分子発生学 頭蓋顎顔面の発生 顔面の組織は発生過程における顔面隆起に由来する
    飯村 忠浩, 江藤 一洋
    The Quintessence 19 1 3 - 9 クインテッセンス出版(株) 2000年01月 [査読無し][通常論文]
  • H Miyazaki, M Fukuda, Y Ishijima, Y Takagi, T Iimura, A Negishi, R Hirayama, N Ishikawa, T Amagasa, N Kimura
    CLINICAL CANCER RESEARCH 5 12 4301 - 4307 1999年12月 [査読無し][通常論文]
     
    The metastasis suppressor activity of nm23/nucleoside diphosphate (NDP) kinase was assessed using human oral squamous cell carcinoma (SCC) cell lines. When the expression of mm23/NDP kinase was compared among several SCC cell lines, nm23-H2/NDP kinase B gene product, but not nm23-H1/NDP kinase A gene product, was reduced in the metastatic cells, Transfection of nm23-H2 into the metastatic SCC cell line LMF4 caused reduction in the lung metastasis in an experimental metastasis assay. A histological analysis of the pulmonary metastatic foci revealed that although foci of the control clones were composed of anaplastic squamous cells, those of the nm23-H2-transfected clones consisted of mostly well-differentiated cells mimicking normal stratified epithelial constitution. The transfected cells were morphologically indistinguishable from the control ones in culture, but they differed from each other in that the former cells proliferated faster than the latter, became less serum dependent, and lost responsiveness to growth factors such as platelet-derived growth factor, insulin-like growth factor I, and insulin, although both clones retained sensitivity to transferrin, These results demonstrate that nm23-H2 protein does have metastasis suppressor activity for human SCC cells and suggest that this activity may be elicited by modulating growth and/or differentiation potential in response to environmental factors.
  • M Goseki-Sone, A Yamada, K Asahi, A Hirota, Ezawa, I, T Iimura
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 265 1 24 - 28 1999年11月 [査読有り][通常論文]
     
    Alkaline phosphatases (ALP) are highly ubiquitous enzymes present in the majority of animals from bacteria to higher vertebrate. Although their wide distribution in nature has suggested that these enzymes should perform important biological functions, their detailed roles or natural substrates remain unknown. In Escherichia coli, the extracellular phosphate (Pi) limitation induces the ALP gene, indicating the role of extracellular Pi in ALP gene regulation. However, little is known about the similar mechanisms in mammalian cells. This study was designed to examine the effect of low Pi medium on the ALP activity and its expression in the mouse stromal cell line ST2. The enzymatic property was classified into tissue-nonspecific ALP (TNSALP). After treatment by Pi starvation for 3 days, there was a a-fold increase in the specific activity of TNSALP. RT-PCR analysis revealed that the mRNA of the TNSALP gene was highly stimulated. These results indicated that the effect of Pi depletion on ALP activity was regulated at the TNSALP transcriptional level, suggesting that the possible role of the Pi sensing system for biological functions of ALP might have been conserved in evolution. Our findings also made it possible to discuss the physiological roles of ALP, in vivo. (C) 1999 Academic Press.
  • S Kuroda, S Kasugai, S Oida, T Iimura, K Ohya, T Ohyama
    BONE 25 4 431 - 437 1999年10月 [査読有り][通常論文]
     
    Fibroblast growth factor 4 (FGF4), a member of the FGF family, plays several important roles in bone development during embryogenesis. Systemic administration of FGF4 increases bone mass in rats, which suggests the potential therapeutic usefulness of this growth factor in treatment for osteopenia and in bone regeneration. We investigated the length of FGF4 required to exert its anabolic effects, because this information may be useful in developing new molecules to mimic the effects of FGF4, Because the active site of FGF family molecules is in the carboxylterminal region, we produced aminoterminally truncated recombinant human FGF4s (rhFGF4s) of different sizes. Humam FGF4 cDNA containing almost the full length of the coding region (573 bp, 191 amino acid residues) was inserted into pUC18 vector and then deleted from the 5' end using the ExoIII system. Each of the deleted FGF4 cDNAs was subcloned into a pET29(+) expression vector. Differently sized recombinant proteins were expressed in the BL21(DE3)pLysS Escherichia coli strain and then purified. The growth-stimulative effects on NIH3T3 cells of each recombinant protein were examined by means of MTT colorimetric assay. Full-length and the shortened recombinant proteins, which stimulated NIH3T3 cell growth, were then subcutaneously administered into male ddY mice (6 weeks old) every day for 2 weeks. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DEXA) and peripheral quantitative computed tomography (pQCT), The rhFGF4 of 134 amino acid residues, the region homologous to other members of the FGF family, exerted a growth-stimulative effect on NIH3T3 cells comparable to the full-length version of FGF4; however, the shortest version, with 111 amino acid residues, showed a limited growth-stimulative effect. Systemic administration of the rhFGF4 of 134 amino acid residues increased the bone mineral density (BMD) of femurs at a dose of 0.1 mg/kg, which was comparable to that of the full-length rhFGF4, DEXA analysis, pQCT analysis, soft X-ray photos, and contact microradiographs revealed an increase in femoral trabecular bone in FGF4-treated animals; an increase in bone formation was also evident upon histomorphometric analysis. These results indicate that the region of FGF4 that is homologous to other FGF family members provides a sufficient anabolic effect in bone and that this recombinant protein is potentially useful as a therapeutic agent in bone, (C) 1999 by Elsevier Science Inc. an rights reserved.
  • 分子発生 神経堤細胞の分布パターンと成長因子に対する応答性の関連性 顔面組織の分化・形態形成を理解する鍵
    飯村 忠浩, 今井 元, 青戸 一司, 江藤 一洋
    口腔病学会雑誌 66 3 295 - 295 口腔病学会 1999年09月 [査読無し][通常論文]
  • H Watanabe, M Goseki-Sone, T Iimura, S Oida, H Orimo, Ishikawa, I
    JOURNAL OF PERIODONTOLOGY 70 6 688 - 691 1999年06月 [査読有り][通常論文]
     
    Hypophosphatasia (HOPS) is an inherited disorder characterized by the defect of skeletal mineralization due to tissue-nonspecific alkaline phosphatase (TNSALP) deficiency. In this study we analyzed the TNSALP gene from a Japanese patient with HOPS, his parents, his brother, and unrelated normal controls. The proband is a 25-year-old Japanese male diagnosed with childhood hypophosphatasia. The patient reported premature exfoliation of the deciduous teeth and severe periodontal destruction of the permanent dentition. Genomic DNA was extracted from peripheral leukocytes of subjects. Eleven pairs of the polymerase chain reaction (PCR) primers were used to amplify the coding exons according to the published sequence data of the TNSALP gene. The PCR amplified samples were subjected to PCR-single strand conformation polymorphism (SSCP) analysis and PCR-allele specific oligonucleotide (ASO) analysis. In PCR-SSCP analysis of the patient's genomic DNA, the fragments containing exons 9 and 10 revealed abnormal mobilities. These abnormal mobilities (exons 9 and 10) were also found from his mother and father's genomic DNA, respectively. The sequencing analysis of the abnormal bands extracted from the SSCP gel showed a T to C transition at nucleotide position 1155 (T1155C) in exon 9 and G1320A in exon 10. PCR-ASO analysis confirmed these missense point mutations. PCR-ASO analysis also confirmed that mutation-specific oligonucleotides corresponded to the new mutations and did not hybridize with PCR products from normal control genomic DNAs. These results indicated that the proband was a compound heterozygote who inherited T1155C mutation in exon 9 from the mother and G1320A mutation in exon 10 from the father: Both of them are new missense point mutations and appear to cause significant changes in the structure and function of TNSALP.
  • WR Duarte, S Kasugai, T Iimura, H Kondo, S Oida, K Takenaga, K Ohya, Ishikawa, I
    JOURNAL OF DENTAL RESEARCH 78 5 1124 - 1124 1999年05月 [査読有り][通常論文]
  • M Goseki-Sone, T Iimura, K Takeda, A Nifuji, Y Ogata, M Yanagishita, S Oida
    CALCIFIED TISSUE INTERNATIONAL 64 2 160 - 162 1999年02月 [査読有り][通常論文]
     
    Tissue-nonspecific-type alkaline phosphatase (TNSALP) is found in the bone, liver, kidney, and other tissues, and its gene consists of 12 exons with the coding sequence beginning in the second exon. Recently, a noncoding first exon was identified in the liver message (liver type) which differed from that of the previously known osteoblast-derived cDNA sequence (bone type). Although these two mRNAs produce an identical protein, they have different promoter regions. It is known that ALPs in dental pulp and periodontal ligament are classified into TNSALP by their enzymatic and immunological properties, but little is known about the expression of ALP mRNAs and the transcriptional mechanisms. In order to examine the expression of their mRNA type, specific oligonucleotide primers corresponding to two types of mRNAs of human TNSALP were designed and amplified by reverse transcription-polymerase chain reaction (RT-PCR). It was found that bone-type mRNA was expressed in the human dental tissues such as dental pulp, periodontal ligament, and dental sec, whereas liver-type mRNA was not expressed. Thus, it was concluded that the human dental tissues express the bone-type isozymes and are regulated by the same transcriptional mechanism as in the bone.
  • WR Duarte, T Iimura, K Takenaga, K Ohya, Ishikawa, I, S Kasugai
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 255 2 416 - 420 1999年02月 [査読有り][通常論文]
     
    S100A4 is a member of the S100 calcium-binding protein family. S100A4 is expressed in several tissues; however, it is secreted by few cell types and its extracellular roles are unknown. In the present study we showed by in situ hybridization that periodontal ligament (PDL) cells express the S100A4 mRNA, Immunolocalization of the S100A4 protein in cryosections of PDL and analyses of PDL cell culture medium revealed that PDL cells secrete the S100A4 protein both in vivo and in vitro. Interestingly, addition of a recombinant mouse S100A4 protein to a bone marrow cell culture inhibited mineralized nodule formation in a concentration-dependent manner. This is the first report of an extracellular role for S100A4 as an inhibitor of mineralization. The PDL space is kept free of mineralization and S100A4 may be one of the factors responsible for such phenomenon. (C) 1999 Academic Press.
  • Wagner Rodrigues Duarte, Yuko Mikuni-Takagaki, Toshio Kawase, Tadahiro Iimura, Shinichiro Oida, Keiichi Ohya, Keizo Takenaga, Isao Ishikawa, Shohei Kasugai
    Journal of Medical and Dental Sciences 46 3 117 - 122 1999年 [査読有り][通常論文]
     
    The periodontal ligament (PDL) functions under constant mechanical stress, and PDL cells obviously control PDL functions under such conditions. We have previously found that the mRNA expression of the Ca 2+-binding protein S100A4 and β-actin is higher in the PDL from erupted teeth than in the PDL from teeth under eruption. This suggested a role for S100A4 in the response of PDL cells to mechanical stress, possibly by coupling Ca 2+ and the cytoskeletal system. In the present study, we investigated the direct effects of cyclical stretching on the mRNA expression of S100A4 and two cytoskeletal components (β-actin and α-tubulin) by PDL cells. In Northern blotting analysis, the expression of S100A4, β-actin, and α-tubulin mRNAs was higher in the PDL from fully erupted and functional bovine teeth than in partially erupted ones. Similarly, when bovine PDL cells were mechanically stimulated by means of the Flexercell Strain Unit, the expression of S100A4, β-actin, and α-tubulin mRNAs increased over the control levels. The results of our present study indicate that S100A4 is involved in the responses of PDL cells to mechanical stress possibly by cou-pling Ca 2+ to the cytoskeletal system in these cells.
  • M Goseki-Sone, H Orimo, T Iimura, H Miyazaki, K Oda, H Shibata, M Yanagishita, Y Takagi, H Watanabe, T Shimada, S Oida
    JOURNAL OF BONE AND MINERAL RESEARCH 13 12 1827 - 1834 1998年12月 [査読有り][通常論文]
     
    Hypophosphatasia (HOPS) is an inherited disorder characterized bg defects in skeletal mineralization due to the deficiency of tissue-nonspecific alkaline phosphatase (TNSALP), To date, various mutations in the TNSALP gene have been identified. Especially, a deletion of T at position 1735 (1735T-del) located in exon 12 has been detected in three genetically unrelated Japanese patients, which seems to be one of the hot spots among the causative mutations in Japanese HOPS patients. 1735T-del causes a frame shift downstream from codon 503 (Leu), and consequently the normal termination codon at 508 is eliminated. Since a new inframe termination codon appears at codon 588 in the mutant DNA, the resultant protein is expected to have 80 additional amino acids. Expression of the mutant TNSALP gene using COS-1 cells demonstrated that the protein translated from the mutant 1735T-del had undetectable ALP activity, and its molecule size was larger than normal, as expected, Interestingly, an inmunoprecipitation study of patients' sera using antibody against TNSALP revealed an abnormal protein which corresponded in size to the mutated TNSALP expressed by COS-1 cells, suggesting that the abnormal TNSALP is made by HOPS patients. The detection of TNSALP in cells transfected with 1735T-del using an immunofluorescent method exhibited only a faint signal on the cell surface, but an intense intracellular fluorescence after permeabilization.
  • Koyama, I, M Yakushijin, M Goseki, T Iimura, T Sato, M Sonoda, S Hokari, T Komoda
    CLINICA CHIMICA ACTA 275 1 27 - 41 1998年07月 [査読有り][通常論文]
     
    The lower levels of serum alkaline phosphatase (AP) activity found in patients with diabetes mellitus apparently originate from the selective disappearance or decrease in bone AP activity in the circulation. Hence, we investigated in vitro the effect of glycation on the activities of five AP isozymes. Aseptic incubation with 25 mmol/L of D-glucose and APs rapidly reduced bone and placental AP activities before those of liver, kidney and intestinal enzymes. The resulting bone and placental AP molecules were clearly glycated, according to the result of aminophenylboronic acid affinity chromatography. Furthermore, Western blotting analysis revealed that the placental AP molecule was fragmented, and its partial cleavage took place at Ala(154) on the AP molecule. Since glycation of serum proteins causes the generation of reactive oxygen species, the effects of reactive oxygen species on placental AP activity were assayed, and the results indicated that hydroxyl radicals might be a major factor for the specific inactivation of AP activities. The reduction in AP activity by incubation with glucose in vitro was reversed by the further addition of catalase. Furthermore, ferrous ion with hydrogen peroxide, which generates hydroxyl radicals, had an inhibitory effect on AP activities. These findings suggest that the reduced AP activity in diabetic patients might result from partial cleavage of the bone AP molecule by reactive oxygen species induced by glycation. (C) 1998 Elsevier Science B.V. All rights reserved.
  • M Goseki-Sone, H Orimo, T Iimura, Y Takagi, H Watanabe, K Taketa, S Sato, H Mayanagi, T Shimada, S Oida
    HUMAN MUTATION 11 S263 - S267 1998年 [査読有り][通常論文]
  • W. R. Duarte, S. Kasugai, T. Iimura, S. Oida, K. Takenaga, K. Ohya, I. Ishikawa
    Journal of Dental Research 77 9 1694 - 1699 1998年 [査読有り][通常論文]
     
    The periodontal ligament (PDL) is a unique tissue that is crucial for tooth function. However, little is known of the molecular mechanisms controlling PDL function. To characterize PDL cells at the molecular level, we constructed a cDNA library from bovine PDL tissue. We then focused on the isolation of S100 calcium-binding proteins (CaBPs), because they mediate Ca2+ signaling and control important cellular processes such as differentiation and metabolism. We screened the PDL cDNA library with a mouse S100A4 cDNA, and cloned the bovine cDNAs of two S100 CaBPs (S100A4 and S100A2). In Northern blotting analysis, the highest expression of S100A4 was detected in PDL from erupted teeth (PDLE). PDL from teeth under eruption (PDLU) showed a lower expression of S100A4, and its expression in gingiva was faintly detectable. S100A4 expression was also high in the pulp tissue followed by the dental papilla of the tooth germ. S100A2 expression was high in PDLE and gingiva. Interestingly, only PDLE exhibited a high expression of both S100A4 and S100A2. PDLE also expressed the highest level of β-actin, a target cytoskeletal protein for S100A4. It is conceivable that the high expression of S100A4 in PDLE is a result of the maturation of the PDL and/or a response to mechanical stress generated by mastication. Since there was a marked difference of S100A4 expression between PDL and gingiva, we propose that S100A4 could be a useful marker for distinguishing cells from these two tissues.
  • Hideo Orimo, Masae Goseki-Sone, Tadahiro Iimura, Yuzo Takagi, Hisashi Watanabe, Kazuhisa Taketa, Seiji Sato, Hideaki Mayanagi, Akira Ohtake, Shinichiro Oida, Takashi Shimada
    Japanese Journal of Human Genetics 42 103  1997年12月 [査読有り][通常論文]
     
    Hypophosphatasia (HOPS) is an autosomal recessive disease with skeretal hypomineralization due to deficiency of tissue-nonspecific alkaline phosphatase (TNSALP). We screened the TNSALP gene in 7 Japanese families with HOPS using PCR-SSCP-direct sequencing method and found 9 novel mutations. E281K, AF310, and frameshifts downstream from S328 and from L503 were found in 3 cases of perinatal/infantile type. F310L and V365I, A160T and F310L were found in a childhood type and an adult type, respectively. A94T, E174G and frameshift from L503 were found in 2 cases of odontohypophosphatasia. Partial intronic sequences of the TNSALP gene were determined to design the PCR primers that amplify whole coding exons. The mutations found in Japanese HOPS were completely different from those in North America and there were no clear relations between the mutation sites and phenotypes.
  • T Iimura, K Takeda, M Goseki, M Maruoka, S Sasaki, S Oida
    DNA SEQUENCE 8 1-2 87 - 92 1997年 [査読有り][通常論文]
     
    Screening of a human dental pulp cells cDNA library with mouse Msx-1 and Msx-2 cDNA probes led to the isolation of human MSX-2. Sequence and Northern Blotting analysis revealed that two different type of transcripts due to the length of 3' untranslated region were expressed in the human dental pulp cells.
  • Noriko Osumi, Arisa Hirota, Hideyo Ohuchi, Masato Nakafuku, Tadahiro Iimura, Shigeru Kuratani, Michio Fujiwara, Sumihare Noji, Kazuhiro Eto
    Development 124 15 2961 - 2972 1997年 [査読有り][通常論文]
     
    Pax-6 is a member of the vertebrate Pax gene family, which is structurally related to the Drosophila pair-rule gene, paired. In mammals, Pax-6 is expressed in several discrete domains of the developing CNS and has been implicated in neural development, although its precise role remains elusive. We found a novel Small eye rat strain (rSey2) with phenotypes similar to mouse and rat Small eye. Analyses of the Pax-6 gene revealed one base (C) insertion in an exon encoding the region downstream of the paired box of the Pax-6 gene, resulting in generation of truncated protein due to the frame shift. To explore the roles of Pax-6 in neural development, we searched for abnormalities in the nervous system in rSey2 homozygous embryos. rSey2/rSey2, exhibited abnormal development of motor neurons in the hindbrain. The Islet-1-positive motor neurons were generated just ventral to the Pax-6-expressing domain both in the wild-type and mutant embryos. However, two somatic motor (SM) nerves, the abducent and hypoglossal nerves, were missing in homozygous embryos, By retrograde and anterograde labeling, we found no SM-type axonogenesis (ventrally growing) in the mutant postotic hindbrain, though branchiomotor and visceral motor (BM/VM)-type axons (dorsally growing) were observed within the neural tube. To discover whether the identity of these motor neuron subtypes was changed in the mutant, we examined expression of LIM homeobox genes, Islet-1, Islet-2 and Lim-3. At the postotic levels of the hindbrain, SM neurons expressed all the three LIM genes, whereas BM/VM-type neurons were marked by Islet-1 only. In the Pax-6 mutant hindbrain, Islet-2 expression was specifically missing, which resulted in the loss of the cells harboring the postotic hindbrain SM-type LIM code (Islet-1 + Islet-2 + Lim-3). Furthermore, we found that expression of Wnt-7b, which overlapped with Pax-6 in the ventrolateral domain of the neural tube, was also specifically missing in the mutant hindbrain, while it remained intact in the dorsal non-overlapping domain. These results strongly suggest that Pax-6 is involved in the specification of subtypes of hindbrain motor neurons, presumably through the regulation of Islet-2 and Wnt-7b expression.
  • Hiroko N. Matsumoto, Asako Yamamoto, Tadahiro Iimura, Shinichiro Oida, Ikuko Ezawa, Satoshi Sasaki, Masae Goseki-Sone
    Journal of Nutritional Science and Vitaminology 43 5 529 - 539 1997年 [査読有り][通常論文]
     
    The aim of this study was to investigate the effects of ovariectomy (OVX) on intestinal alkaline phosphatase (ALP) activity in rats. The calcium (Ca) and phosphorus (P) contents and the mechanical strength of bone were decreased significantly by OVX. Two kinds of mRNAs of rat intestinal ALP (RTIN-1 and RTIN-2) were detected by reverse transcription-polymerase chain reaction (RT-PCR). In OVX rats, the level of RTIN-2 mRNA was lowered significantly, while that of RTIN-1 mRNA did not change. This result was compatible with the results of enzymatic activity. This finding suggests the possibility that OVX affects bone metabolism not only directly but also in an indirect way through an intestinal Ca and/or P metabolism via regulation of intestinal RTIN-2 ALP expression.
  • Tadahiro Iimura, Kohsuke Takeda, Masae Gosekp, Yutaka Maruoka, Satoshi Sasaki, Shinichro Oida
    Mitochondrial DNA 8 1-2 87 - 92 1997年 [査読有り][通常論文]
     
    Screening of a human dental pulp cells cDNA library with mouse Msx-1 and Msx-2 cDNA probes led to the isolation of human MSX-2. Sequence and Northern Blotting analysis revealed that two different type of transcripts due to the length of 3′ untranslated region were expressed in the human dental pulp cells. © 1997 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
  • M GosekiSone, S Oida, T Iimura, A Yamamoto, HN Matsumoto, N Omi, K Takeda, Y Maruoka, Ezawa, I, S Sasaki
    LIVER 16 6 358 - 364 1996年12月 [査読有り][通常論文]
     
    The presence of types of alkaline phosphatase (ALP) other than the tissue non-specific type enzyme in rat liver and its increase by fat feeding are known. In order to examine expression of intestinal type ALP in liver, specific oligonucleotide primers corresponding to two types of mRNAs of rat intestinal ALP (RTIN-1 and -2) were designed and amplified by means of the reverse transcriptase-polymerase chain reaction (RT-PCR). It was found that RTIN-1 mRNA was expressed only in the intestine but not in the Liver, while RTIN-2 mRNA was expressed both in the intestine and in the liver. By fat feeding, expression of RTIN-1 mRNA increased in the intestine and that of RTIN-2 mRNA increased both in the intestine and in the liver. Thus, it was concluded that rat liver expressed one of the intestinal type ALP (RTIN-2) which was enhanced by fat feeding.
  • Y Niinaka, SI Oida, A Ishisaki, K Takeda, T Iimura, Y Maruoka, F Momose, A Negishi, H Ichijo, T Amagasa, S Sasaki, H Watanabe, A Raz
    INTERNATIONAL JOURNAL OF ONCOLOGY 9 3 433 - 438 1996年09月 [査読有り][通常論文]
     
    Autocrine motility factor (AMF) a tumor-secreted 55 kDa cytokine induces tumor cell motility by a signal transduction pathway mediated by interaction with its receptor (AMFR) a cell surface glycoprotein of 78 kDa (gp78). Here, AMF secreted by the metastatic LMF4 human oral squamous-cell carcinoma (SCC) cells, induced dose- and time-dependent morphological changes and chemotaxis of the producing cells. Expression of AMFR mRNA was associated with the metastatic ability of SCC cell variants. The data presented show for the first time that SCC cells produce AMF and express AMFR and the expression is related to their invasiveness and metastatic potentials.
  • S Oida, H Miyazaki, T Iimura, M Suzuki, S Sasaki, H Shimokawa
    DNA SEQUENCE 6 5 307 - 310 1996年 [査読無し][通常論文]
     
    A genomic DNA clone (14.5 kbp) for amelogenin, a tooth enamel specific protein, has been isolated from a mouse genomic library. The nucleotide structure of this DNA was determined by the polymerase chain reaction and sequence analysis. The result indicated that the cloned DNA contained all the exons in addition to approximately 5.5 kbp of upstream sequence.
  • T IImura, O Baba, Y Maruoka, K Takeda, S Sasaki, H Shimokawa, S Oida
    MOLECULAR AND DEVELOPMENTAL BIOLOGY OF CARTILAGE 785 274 - 277 1996年 [査読有り][通常論文]
  • Shinichiro Oida, Hidetaka Miyazaki, Tadahiro Iimura, Michiko Suzuki, Satoshi Sasaki, Hitoyata Shimokawa
    Mitochondrial DNA 6 5 307 - 310 1996年 [査読有り][通常論文]
     
    A genomic DNA clone (14.5 kbp) for amelogenin, a tooth enamel specific protein, has been isolated from a mouse genomic library. The nucleotide structure of this DNA was determined by the polymerase chain reaction and sequence analysis. The result indicated that the cloned DNA contained all the exons in addition to approximately 5.5 kbp of upstream sequence. © 1996 Informa UK Ltd All rights reserved.
  • Molecular cloning of mouse amelogenin genes from mandibular cDNA library
    S.Oida, T.Iimura, N.Arai, K.Takeda, A.Ishikawa, Y.Maruoka, T.Tarashima, H.Shimokawa, S.Sasaki
    J Hard Tissue Biol 42 2 64 - 69 1995年 [査読無し][通常論文]
  • S OIDA, T IIMURA, Y MARUOKA, K TAKEDA, S SASAKI
    DNA SEQUENCE 5 5 273 - 275 1995年 [査読無し][通常論文]
     
    A cDNA clone encoding bone morphogenetic protein-4 (BMP-4) has been,isolated from a human placental cDNA library. Sequence analysis of this clone revealed that the nucleotide sequence of 5' region was different from that of human osteosarcoma BMP-4 and the deduced amino acid sequence indicated deletion of N-terminal 6 amino acids. We confirmed the expression of this type of BMP-4 mRNA in one human osteogenic cell line in addition to the placenta by the polymerase chain reaction (PCR).
  • T IIMURA, S OIDA, K TAKEDA, Y MARUOKA, H SHIMOKAWA, K IBARAKI, S SASAKI
    DNA SEQUENCE 5 4 233 - 237 1995年 [査読無し][通常論文]
     
    Screening of a bovine odontoblast cDNA library from developing incisor with murine Msx-1 and Msx-2 cDNA probes led to the isolation of three positive clones. All of them encoded for a sequence of a protein containing 297 amino acids. The responsible gene was designated as bovine Msx-1 (bMsx-1) due to the high homology with the human MSX-1 and mouse Msx-1 sequences.
  • Tadahiro Iimura, Shinichiro Oida, Kohsuke Takeda, Yutaka Maruoka, Hitoyata Shimokawa, Kyomi Ibaraki, Satoshi Sasaki
    Mitochondrial DNA 5 4 233 - 237 1995年 [査読有り][通常論文]
     
    Screening of a bovine odontoblast cDNA library from developing incisor with murine Msx-1 and Msx-2 cDNA probes led to the isolation of three positive clones. All of them encoded for a sequence of a protein containing 297 amino acids. The responsible gene was designated as bovine Msx-1 (bMsx-1) due to the high homology with the human MSX-1 and mouse Msx-1 sequences. © 1995 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
  • M GOSEKI, S OIDA, K TAKEDA, Y OGATA, T IIMURA, Y MARUOKA, S SASAKI
    JOURNAL OF DENTAL RESEARCH 74 1 319 - 322 1995年01月 [査読有り][通常論文]
     
    Tissue-nonspecific-type alkaline phosphatase is found in the bone, liver, kidney, and other tissues, and its gene consists of 12 exons with the coding sequence beginning in the second exon. Recently, an alternative non-coding first exon was identified in the liver message which differed from that of the previously known osteoblast-derived cDNA sequence. Although these two mRNAs produce an identical protein, they have different promoter regions. The periodontal ligament tissue expresses a high level of alkaline phosphatase activity. To identify its mRNA type, we isolated a full-length cDNA for alkaline phosphatase from a cultured human periodontal ligament cell expression library, using bone-derived tissue-nonspecific alkaline phosphatase cDNA as a hybridization probe. The size of this clone was 2.5 kb, and its 5' and 3' untranslated sequences were identical to those of the human tissue-nonspecific type isolated from osteoblastic cells but not to those of the Liver type. In addition, the same fragments as in bone-derived tissue-nonspecific-type cDNA were detected by the treatment of the cDNA clone with restriction enzymes Hinc II and Pst I. The results suggest that expression of the same alkaline phosphatase isozyme in human periodontal ligament cells may be regulated by the same transcriptional mechanism as in bone.
  • S. Kasugai, S. Oida, T. Iimura, N. Arai, K. Takeda, K. Ohya, S. Sasaki
    Bone 17 1 1 - 4 1995年 [査読有り][通常論文]
     
    Prostaglandin (PG) E2 displays physiological and pharmacological action in various tissues including bone. It increases intracellular Ca, and stimulates or inhibits CAMP production through the PGE receptor subtypes EP1 EP2, and EP3 respectively. These receptor subtypes have been recently cloned. In the present study, we investigate the expression of these receptor subtypes in bone tissue. RT-PCR revealed that EP1 EP2, and EP3 were expressed in rat calvariae and that osteoblastic cells (MC3T3-E1) expressed EP1 and EP2. In situ hybridization analysis using cryosection of neonatal calvariae revealed that EP2 was expressed by osteoblasts and cells not in contact with bone, probably including preosteoblasts. EP2 expression was observed at an early stage in calvarial development, at 14 days prenatal. EP2 expression was also observed at day 3 in rat bone marrow cell culture in which bone-like mineralized nodules are formed at day 8. It has been established that PGE2 response accompanying cAMP production is one of the characteristics of osteoblasts. The present results indicate that this phenotype appears at an early stage of osteoblastic differentiation and bone development. © 1995.
  • Shinichiro Oida, Tadahiro Iimura, Yutaka Maruoka, Kohsuke Takeda, Satoshi Sasaki
    Mitochondrial DNA 5 5 273 - 275 1995年 [査読有り][通常論文]
     
    A cDNA clone encoding bone morphogenetic protein-4 (BMP-4) has been isolated from a human placental cDNA library. Sequence analysis of this clone revealed that the nucleotide sequence of 5' region was different from that of human osteosarcoma BMP-4 and the deduced amino acid sequence indicated deletion of N-terminal 6 amino acids. We confirmed the expression of this type of BMP-4 mRNA in one human osteogenic cell line in addition to the placenta by the polymerase chain reaction (PCR). © 1995 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
  • Y. Maruoka, S. Oida, T. Iimura, K. Takeda, I. Asahina, S. Enomoto, S. Sasaki
    Biochemistry and Molecular Biology International 35 5 957 - 963 1995年 [査読有り][通常論文]
     
    A clone of a human Bone Morphogenetic Protein-2 (hBMP-2) cDNA was obtained from a cDNA library established from human dental pulp cells. After subcloning hBMP-2 cDNA into Autographa californica nuclear polyhedrosis virus, the recombinant baculovirus was transfected to Sf-9 cells. Immuno-reactive recombinant hBMP-2 (rhBMP-2) was detected by a polyclonal antibody against Xenopus BMP-2 in the transfected insect cells but not in the culture media. Three days after treatment with the lysate of the transfected Sf-9 cells, increase in alkaline phosphatase activity of a murine stromal cell line, ST2, was detected. Subcutaneous implantation of rhBMP-2 produced in the insect cells induced formation of cartilage, bone and bone marrow in the rats. The present data indicated that the rhBMP-2 preparation produced in the insect Sf-9 cells had a comparable activity to that produced in mammalian cells.
  • T. Iimura
    Kokubyo Gakkai zasshi. The Journal of the Stomatological Society, Japan 61 590 - 604 1994年12月01日 [査読無し][通常論文]
     
    Although much is known about the hormonal regulation of hard tissue development, much less is known about the nuclear regulatory molecules that affect the process. Homeobox-containing genes are thought to encode DNA-binding transcriptional factors which control the expression of other genes. In this study, molecular cloning of Msx homeobox-containing genes from a bovine odontoblast library and a human dental pulp-derived cells library was performed, and also the expression of mRNAs for Hox and Msx homeobox-containing genes during ectopic bone formation induced by BMP was investigated. Screening of a bovine odontoblast cDNA library and a human dental pulp-derived cells library with murine Msx-1 and Msx-2 cDNA probes led to the isolation of several positive clones. All of the clones from a bovine odontoblast library encoded the bovine counterpart for human MSX-1. All of the clones from a human dental pulp-derived cells library encoded the human counterpart for murine Msx-2. Northern blot analysis probed with a human MSX-2 cDNA indicated the expression of 2.2kb and 1.2kb mRNA in human dental pulp-derived cells. Polymerase chain reaction (PCR)-based analysis in the BMP-implanted tissue revealed that nine rat homologues of Hox homeobox-containing genes were expressed in the early cell migration stage and that two Msx genes were expressed in the cartilage and bone differentiation stages. The PCR study provided evidence of dynamic changes in the BMP-induced homeobox gene expression.
  • K TAKEDA, S OIDA, H ICHIJO, T IIMURA, Y MARUOKA, T AMAGASA, S SASAKI
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 204 1 203 - 209 1994年10月 [査読有り][通常論文]
     
    A cDNA for the rat bone morphogenetic protein (BMP) type IA receptor (BMPR-IA) was isolated from a dental pulp cell cDNA library. The rat BMPR-IA cDNA encodes a protein of 532 amino acids with a single transmembrane domain and a putative serine/threonine kinase domain. The overall amino acid sequence identity between the rat and human BMPR-IA was 97 %. Reverse transcriptase-polymerase chain reaction analysis revealed that BMPR-IA mRNA was highly expressed in the BMP-induced bone forming tissues throughout the stages tested. (C) 1994 Academic Press, Inc.
  • T. Iimura, S. Oida, H. Ichijo, M. Goseki, Y. Maruoka, K. Takeda, S. Sasaki
    Biochemical and Biophysical Research Communications 204 2 918 - 923 1994年10月 [査読有り][通常論文]
     
    The effect of TGF-beta 1 on the expression of alkaline phosphatase (ALPase) activity was examined during osteoblastic cell line (MG-63) differentiation induced by 1,25-dihydroxyvitamin D-3(1,25D(3)). TGF-alpha 1 and 1.25D(3) were found to enhance ALPase activity. However, preincubation of the cells with 1,25D(3) transiently abolished the effects of TGF-beta 1. Kinetics of the complex responses to TGF-beta 1 and 1,25D(3) were found to correlate well with that of the expression level of type II receptor for TGF-beta. These results suggest that 1,25D(3) may regulate the cellular responses to TGF-beta 1 in part via regulation of functional receptor for TGF-beta (C) 1994 Academic Press, Inc.
  • T IIMURA, S OIDA, K TAKEDA, Y MARUOKA, S SASAKI
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 201 2 980 - 987 1994年06月 [査読有り][通常論文]
     
    Expression of homeobox genes in relation to ectopic bone formation induced by bone morphogenetic protein (BMP) was investigated. Oligonucleotide primers corresponding to highly conserved regions of Hox cluster and Msx genes were designed to detect homeobox sequences by means of the polymerase chain reaction (PCR). Nine rat homologues of Hox duster genes and two Msx genes were discovered in the BMP-implanted tissue, at earlier stage and later cartilage and bone formation stage, respectively. The PCR study provided evidence of dynamic changes in BMP-induced homeobox gene expression. (C) 1994 Academic Press, Inc.
  • K. Takeda, S. Oida, M. Goseki, T. Iimura, Y. Maruoka, T. Amagasa, S. Sasaki
    Bone 15 5 467 - 470 1994年 [査読有り][通常論文]
     
    Dental pulp has a potential to induce ectopic bone formation, but little is known about its mechanism. We thought that bone morphogenetic proteins (BMPs), members of the transforming growth factor-β (TGF-β) superfamily, are involved in the osteoinductive activity of dental pulp. In order to prove this assumption, we constructed a cDNA library from primary culture cells of human dental pulp (HDP cells), and screened the library with previously cloned cDNAs for mouse BMP-2 and -6 as probes. Three distinct cDNA clones encoding human BMP-2, -4 and -6 were isolated. By Northern blot analysis, specific transcripts of the genes of those BMPs were detected in the HDP cells. It was concluded that the BMPs were expressed in a certain population of dental pulp cells and might play some roles in ectopic bone formation by dental pulp. © 1994.
  • S.Oida, A.Nifuji, M.Tamura, Y.Maruoka, T.Iimura, S.Sasaki
    Jpn J Oral Biol 34 5 612 - 615 1992年 [査読無し][通常論文]
  • Fluorescent imaging approach and perspective for the circadian development and metabolism of bone
    Nakane A, Numano R, Takagi Y, Yamaguchi A, Iimura T
    Jounal of Bone Morphometry. 23 41 - 50 [査読有り][通常論文]

書籍

  • 愛媛大学「研究室からこんにちは!」10
    飯村 忠浩 (担当:分担執筆範囲:画像によるライブイメージングで発生生物学を研究・がん診断などの応用が期待できるHox遺伝子)
    アトラス出版 2016年
  • 骨ペディア 骨疾患・骨代謝キーワード事典
    飯村 忠浩 (担当:分担執筆範囲:第6章 keyword 21 「ケモカイン」)
    羊土社 2015年
  • 口腔組織・発生学 (改訂 新版)
    飯村 忠浩 (担当:分担執筆範囲:蛍光バイオイメージング)
    医歯薬出版 2015年
  • Key Word 1996-97 炎症免疫系
    飯村 忠浩 (担当:分担執筆範囲:Hox 遺伝子)
    先端医学社 1996年
  • 実験医学別冊・骨粗鬆症-分子メカニズムから病態,診断,治療まで
    飯村 忠浩 (担当:分担執筆範囲:骨基質タンパク、ハイドロキシアパタイトと石灰化骨、類骨)
    羊土社 1995年

講演・口頭発表等

  • 口腔と全身の運動器薬理学研究  [通常講演]
    飯村 忠浩
    北海道大学大学院歯学研究院セミナー 2018年12月
  • CC ケモカイン受容体のゲノム進化と骨代謝における病態機能解析  [通常講演]
    飯村 忠浩
    日仏生物学会第 189 回例会 2018年12月
  • 骨組織・細胞の形態学的観察法−光学顕微鏡の基礎から論文映えする写真の撮り方−  [招待講演]
    飯村 忠浩
    第36回日本骨代謝学会学術集会 2018年07月
  • 骨Ontogenyの学際的理解の追求  [招待講演]
    飯村 忠浩
    第36回日本骨代謝学会学術集会 2018年07月
  • マルチモード蛍光観察による新規の骨代謝病態機能探索  [招待講演]
    飯村 忠浩, 李 智媛
    第123回日本解剖学会総会・全国学術集会 2018年03月
  • ドラッグ・リポジョショニングとプロテオ創薬 による骨代謝改善標的分子の探索  [招待講演]
    飯村 忠浩
    第410/411回 北海道歯学会例会 2017年12月
  • 超解像イメージングによる骨系細胞の微細構造と動態機能解析  [招待講演]
    飯村 忠浩
    第44回日本臨床バイオメカニクス学会 2017年11月
  • HIV治療標的分子CCR5の 骨代謝における役割  [招待講演]
    飯村 忠浩
    遺伝子病制御研究所 血管生物学セミナー 2017年11月
  • 運動器研究における組織・細胞の形態学的観察法−私なら、こうする−  [招待講演]
    飯村 忠浩
    日本骨代謝学会 Skeletal Science Retreat 2017 2017年10月
  • 骨代謝のマルチモード・イメージング解析  [招待講演]
    飯村 忠浩
    日本顕微鏡学会 平成29年度関西支部特別講演会 2017年10月
  • マウスジェネティクスを用いたHIV感染患者の骨病態解明  [招待講演]
    飯村 忠浩, 李 智媛
    第59回歯科基礎医学会学術大会 2017年09月
  • 骨粗鬆症治療薬の育薬研究  [招待講演]
    飯村 忠浩
    第24回NPO法人 東京血管疾患研究所セミナー 2017年07月
  • 産学および分野横断連携研究の取り組みと成果  [招待講演]
    飯村 忠浩
    第71回日本口腔科学会学術集会 2017年04月
  • 先進光学顕微鏡の骨形態計測法への応用展開  [招待講演]
    飯村 忠浩
    第122回日本解剖学会総会・全国学術集会 2017年03月
  • 超解像顕微鏡の生物医学応用「ここまで微細に、こんなに綺麗に見える!」  [招待講演]
    飯村 忠浩
    第57回日本組織細胞化学会総会・学術集会 2016年09月
  • 硬組織の形態・機能解析のための光学顕微鏡のマルチモードな活用法−微分干渉から先進レーザー顕微鏡の応用例−  [招待講演]
    飯村 忠浩, 李 智媛
    第58回歯科基礎医学会学術大会 2016年08月
  • マルチモーダル超解像法を用いた骨系細胞の機能解析  [招待講演]
    飯村 忠浩, 李 智媛
    第58回歯科基礎医学会学術大会 2016年08月
  • 副甲状腺ホルモン:PTHの分子シグナルと薬理効果  [招待講演]
    飯村 忠浩
    第34回日本骨代謝学会学術集会 / 第3回アジア太平洋骨代謝学会議 2016年07月
  • 副甲状腺ホルモン:PTHの基礎生物医学-最近の知見から-  [招待講演]
    飯村 忠浩
    第35回長崎骨粗鬆症研究会 2016年06月
  • 医理工融合研究センターにおける学際的研究の推進−異分野融合は異文化融合−  [招待講演]
    飯村 忠浩
    第70回日本口腔科学会学術集会 2016年04月
  • 骨形成の超解像イメージング解析  [招待講演]
    飯村 忠浩
    第121回日本解剖学会総会・全国学術集会 2016年03月
  • ライブイメージングと数理計測で見る脊椎動物の発生ボディプランの調節機構  [招待講演]
    飯村 忠浩
    第57回歯科基礎医学会学術大会 2015年09月
  • 骨吸収の促進は骨細胞におけるsclerostinの発現を低下させ、Wnt/β-cateninシグナルを促進する  [通常講演]
    小出 雅則, 小林 泰浩, 山下 照仁, 上原 俊介, 飯村 忠浩, 中村 美どり, 高橋 直之, 宇田川 信之, 保田 尚孝
    Journal of Oral Biosciences Supplement 2015年09月
  • 骨の細胞イメージング-a new horizon-骨のメカニズムをどこまで観ることができるか 蛍光細胞イメージングと骨形態計測で見る骨代謝におけるケモカインシグナルの役割  [通常講演]
    李 智媛, 飯村 忠浩
    Journal of Oral Biosciences Supplement 2015年09月
  • 生体機能の多次元バイオイメージング ライブイメージングと数理計測で見る脊椎動物の発生ボディプランの調節機構  [通常講演]
    飯村 忠浩
    Journal of Oral Biosciences Supplement 2015年09月
  • 二光子励起顕微鏡を用いた軟骨変性の評価  [通常講演]
    清松 悠, 大嶋 佑介, 斎藤 卓, 疋田 温彦, 三浦 裕正, 宮崎 剛, 飯村 忠浩, 今村 健志
    日本整形外科学会雑誌 2015年09月
  • 骨吸収の促進は骨細胞におけるsclerostinの発現を低下させ、骨形成を促進する  [通常講演]
    小出 雅則, 小林 泰浩, 山下 照仁, 上原 俊介, 尾崎 友輝, 飯村 忠浩, 中村 美どり, 保田 尚孝, 高橋 直之, 宇田川 信之
    日本骨代謝学会学術集会プログラム抄録集 2015年07月
  • 骨関連細胞ネットワークin vitro再構築系の2光子励起顕微鏡による解析  [通常講演]
    疋田 温彦, 飯村 忠浩, 大嶋 佑介, 今村 健志
    日本骨代謝学会学術集会プログラム抄録集 2015年07月
  • マルチスケール画像解析の骨生物医学への応用展開  [通常講演]
    飯村忠浩, 李 智媛
    第35回日本骨形態計測学会 2015年06月
  • 骨代謝関連細胞ネットワークin vitro再構築系の2光子イメージング  [通常講演]
    疋田 温彦, 飯村 忠浩, 大嶋 佑介, 齋藤 卓, 山本 真, 今村 健志
    日本骨形態計測学会雑誌 2015年05月
  • 骨バイオイメージングの新たな展開 マルチスケール画像解析の骨生物医学への応用展開  [通常講演]
    飯村 忠浩, 李 智媛
    日本骨形態計測学会雑誌 2015年05月
  • 骨バイオイメージングの新たな展開 第二次高調波発生(SHG)イメージングによる軟骨変性の定量的・組織学的評価法の開発  [通常講演]
    大嶋 佑介, 清松 悠, 齋藤 卓, 三浦 裕正, 飯村 忠浩, 今村 健志
    日本骨形態計測学会雑誌 2015年05月
  • 蛍光3次元計測で見る骨細胞の機能的ヘテロジェニティ  [招待講演]
    飯村 忠浩
    第7回骨・軟骨フロンティア 2014年11月
  • DMP1は骨細胞におけるFGF23産生の抑制因子である 蛍光3次元形態計測と細胞生物学的アプローチ  [通常講演]
    李 智媛, 山口 朗, 飯村 忠浩
    日本骨代謝学会学術集会プログラム抄録集 2014年07月
  • 骨代謝研究領域におけるバイオイメージング技術の発展からその応用まで ラマン分光・イメージング技術の開発と骨代謝研究への応用  [通常講演]
    大嶋 佑介, 飯村 忠浩, 疋田 温彦, 今村 健志
    日本骨代謝学会学術集会プログラム抄録集 2014年07月
  • 骨代謝のダイナミクスの新たな潮流 ケモカイン受容体CX3CR1の骨代謝における役割  [通常講演]
    飯村 忠浩, 山口 朗
    日本骨代謝学会学術集会プログラム抄録集 2014年07月
  • Retrieval of regulatory mode of G1/S transition in vertebrate axial development by quantitative live imaging and mathematical models  [招待講演]
    飯村 忠浩
    The 37th Naito Conference 2014年06月
  • Fluorescence morphometric analysis of mechano-sensing osteocytes in bone  [招待講演]
    飯村 忠浩
    International Symposium on Mechanobiology 2014 2014年05月
  • 中軸骨格形態形成の観察と計算モデル  [通常講演]
    齋藤 卓, 今村 健志, 飯村 忠浩
    日本骨形態計測学会雑誌 2014年05月
  • 医歯工連携シンポジウム 画像イメージングと骨形態計測の接点 骨細胞の機能的3次元蛍光計測  [通常講演]
    飯村 忠浩
    日本骨形態計測学会雑誌 2014年05月
  • 医歯工連携シンポジウム 画像イメージングと骨形態計測の接点 ラマン分光分析を基盤とした骨質計測技術の開発  [通常講演]
    大嶋 佑介, 飯村 忠浩, 疋田 温彦, 今村 健志
    日本骨形態計測学会雑誌 2014年05月
  • 医歯工連携シンポジウム 画像イメージングと骨形態計測の接点 骨・軟骨組織の2光子励起顕微鏡・第2次高調波発生を用いた観察  [通常講演]
    疋田 温彦, 大嶋 佑介, 清松 悠, 飯村 忠浩, 今村 健志
    日本骨形態計測学会雑誌 2014年05月
  • 中軸骨格の形態発生の分子基盤 蛍光イメージングで見るボディプランと骨形態疾患  [通常講演]
    飯村 忠浩
    松本歯学 2013年12月
  • 椎間板発生における転写因子Pax1の役割の検討  [通常講演]
    牧野 祐司, 玉村 禎宏, 金子 和夫, 山口 朗, 飯村 忠浩
    日本整形外科学会雑誌 2013年08月
  • 椎間板軟骨の初期発生におけるPax1の役割  [通常講演]
    牧野 祐司, 金子 和夫, 山口 朗, 飯村 忠浩
    日本骨代謝学会学術集会プログラム抄録集 2013年05月
  • 3次元蛍光イメージング法による骨発達の分子メカニズムの探索  [通常講演]
    飯村 忠浩
    日本口腔科学会雑誌 2013年01月
  • 蛍光3次元イメージング形態計測によるSclerostinの時空間的発現変化と生後骨発達における役割  [通常講演]
    渡辺 高, 山口 朗, 飯村 忠浩
    Journal of Oral Biosciences Supplement 2012年09月
  • 異骨症モデルマウスを用いた骨格発生と病態の時空間的解析  [通常講演]
    飯村 忠浩
    Journal of Oral Biosciences Supplement 2012年09月
  • 脊椎肋骨異骨症・脊椎胸郭異骨症の発生病因 Mesp2-nullマウスの解析  [通常講演]
    牧野 祐司, 高橋 雄, 玉村 禎宏, 田辺 里枝子, 祓川 摩有, 五関 正江, 根, 菅野 純, 金子 和夫, 山口 朗, 飯村 忠浩
    日本整形外科学会雑誌 2012年08月
  • 口腔癌による骨破壊では間質細胞と癌細胞の両者が産生するRANKLが重要である  [通常講演]
    佐藤 潔, 李 智媛, 飯村 忠浩, 保田 尚孝, 伊東 昌子, 小村 健, 山口 朗
    日本骨代謝学会学術集会プログラム抄録集 2012年07月
  • 低分子量Gタンパク質Cdc42は四肢形成における軟骨分化と肢芽指間部の細胞死に必須である  [通常講演]
    相澤 怜, 山田 篤, 鈴木 大, 飯村 忠浩, 山本 剛, 山口 朗, 山本 松男, 上條 竜太郎
    日本骨代謝学会学術集会プログラム抄録集 2012年07月
  • Bone Biologyの新機軸 3次元蛍光イメージグと計測で見る骨格の発生異常と骨の発達のメカニズム  [通常講演]
    飯村 忠浩, 山口 朗
    日本骨代謝学会学術集会プログラム抄録集 2012年07月
  • 3次元蛍光光イメージングによる骨の発達メカニズムと骨代謝研究  [招待講演]
    飯村 忠浩
    第68回日本顕微鏡学会学術講演会 2012年05月
  • モデルマウスを用いた脊椎肋骨異骨症および脊椎胸郭異骨症の病因解析  [通常講演]
    牧野 祐司, 高橋 雄, 玉村 禎宏, 田辺 里枝子, 祓川 摩有, 五関 正江, 根, 波多 賢二, 米田 俊之, 菅野 純, 金子 和夫, 山口 朗, 飯村 忠浩
    日本骨形態計測学会雑誌 2012年05月
  • 蛍光3次元イメージング形態計測によるSclerostinの時空間的発現変化の定量的解析と生後骨発達における役割  [通常講演]
    飯村 忠浩, 渡辺 高, 牧野 祐司, 金子 和夫, 天笠 光雄, 山口 朗
    日本骨形態計測学会雑誌 2012年05月
  • 蛍光3次元イメージング形態計測による頭頂骨と長管骨の骨細胞ネットワークの構造の定量的比較  [通常講演]
    飯村 忠浩, 山口 朗
    日本骨形態計測学会雑誌 2012年05月
  • 骨芽細胞分化と骨形成における骨芽細胞特異的転写因子の細胞内局在変化 蛍光イメージングによる解析  [通常講演]
    渡辺 高, 天笠 光雄, 山口 朗, 飯村 忠浩
    日本口腔科学会雑誌 2012年01月
  • Cdc42は四肢形成における軟骨形成と肢芽指間域のアポトーシスを制御する  [通常講演]
    相澤 怜, 山田 篤, 鈴木 大, 塚崎 雅之, 山本 剛, 飯村 忠浩, 山口 朗, 山本 松男, 上條 竜太郎
    Journal of Oral Biosciences 2011年09月
  • Multi-dimensional fluorescence imaging approaches for embryonic development and bone biology  [招待講演]
    飯村 忠浩
    8th Meeting of Bone Biology Forum 2011年08月
  • 脊椎肋骨異骨症(SCDO)2型モデルMesp2(-/-)マウスの椎体における骨・軟骨組織の発生・分化過程の解析 分節時計は椎体と椎間板の規則的空間配置に必須である  [通常講演]
    牧野 祐司, 田辺 里枝子, 波多 賢二, 五関 正江, 根, 金子 和夫, 山口 朗, 飯村 忠浩
    日本骨代謝学会学術集会プログラム抄録集 2011年07月
  • 矯正力による歯の移動における骨細胞の役割  [通常講演]
    松本 力, 飯村 忠浩, 山口 朗
    日本骨形態計測学会雑誌 2011年05月
  • 定量的in situ蛍光イメージングによる骨芽細胞特異的転写因子の骨組織内での分布と細胞内局在の変化の観察  [通常講演]
    渡辺 高, 天笠 光雄, 山口 朗, 飯村 忠浩
    日本骨形態計測学会雑誌 2011年05月
  • 骨の成長と代謝における概日リズムの働き 蛍光イメージングによるアプローチと展望  [通常講演]
    中根 綾子, 沼野 利佳, 佐藤 博紀, 高木 裕三, 山口 朗, 飯村 忠浩
    日本骨形態計測学会雑誌 2011年05月 
    骨と軟骨の代謝における様々な機能が24時間の周期性パターンを示す事は、ゲノム研究が盛んになる前の1960年代から報告されてきた。初期の研究は組織学的なアプローチが主であった。その後、ヒトの骨代謝関連ホルモンやマーカーの血清レベルが日内変動を示すことが次々と明らかにされてきた。分子クローニング技術の飛躍的進歩により、1990年代終盤には、いくつもの時計遺伝子の一次構造および機能が解明された。その後、転写因子のフィードバックループモデルがリズム中枢として働いている事が提唱され、哺乳類の時計中枢として知られている視交叉上核のみならず、様々な末梢組織においても概日リズムを刻む機構が働いていることが明らかとなってきた。骨の成長と代謝もまた、他の末梢組織と同様に、24時間周期の分子機構によって調節されている事が報告されている。さらに、ポストゲノム解析として、マイクロアレイによるトランスクリプトーム解析や、発光・蛍光のシグナルを用いたバイオイメージングによる時空間的な解析が、さらなる総合的な時計遺伝子群の機能解明のために開発されてきた。臨床的には、骨粗鬆症のような骨代謝疾患に対してより効果的な治療成績を見込んだ薬物投与の時期の決定など、概日リズムと骨に関する知見は重要となってきている。本稿では、骨の生物医学における24時間周期の機能調節に関するトピックをレビューし、最新の蛍光イメージングによるアプローチが骨の生物医学分野にどのように貢献していくのか、その可能性について展望を試みたい。(著者抄録)
  • 骨の形態的解析法の進歩 骨のin vivo蛍光イメージングの現状と展望  [通常講演]
    飯村 忠浩, 中根 綾子, 姫野 彰子, 杉山 真由, 山口 朗
    日本骨形態計測学会雑誌 2011年05月 
    骨組織を対象にした"イメージング"研究が話題になりつつある。もっとも硬い組織である骨に最新の光を当てて何がわかってきたのか?本稿では、骨格系の発生や骨組織を対象とした蛍光イメージング観察のトピックスを上げ、「骨のin vivo蛍光イメージング」の現状報告とその展望について議論する。(著者抄録)
  • 脊椎動物の発生におけるライブイメージング(Illumination of vertebrate development by fluorescence live imaging)  [通常講演]
    飯村 忠浩, 杉山 真由, 牧野 祐司, 中根 綾子, 渡辺 高, 山口 朗
    Cytometry Research 2011年03月 
    個体発生は細胞の増殖や移動、機能分化が動的に協調して変遷していく過程である。分子生物学やゲノム科学の進展によって、脊椎動物の発生に関わる様々な共通ルールが明らかとなってきた。蛍光ライブイメージングは、4次元での定量的な解析を可能にし、分子から細胞、組織、器官、個体までのより包括的な理解を助ける。これによって、発生・発達生物医学は、分子の階層的記述から、より動的に理解することが可能になってきた。本稿では、脊椎動物の発生・発達生物医学における最近のトピックをいくつか挙げ、その動向と今後の展望について議論したい。(著者抄録)
  • 骨組織の細胞機能イメージング法による新規の機能解析  [通常講演]
    飯村 忠浩
    Journal of Oral Biosciences 2010年09月
  • Hox遺伝子群と分節時計による脊椎動物の発生基盤  [招待講演]
    飯村 忠浩
    4回北海道大学若手研究者交流会 2010年07月
  • 骨代謝におけるケモカイン受容体CCR1の機能解析  [通常講演]
    星野 昭芳, 飯村 忠浩, 山本 健二, 山口 朗
    日本骨代謝学会学術集会プログラム抄録集 2010年07月
  • 骨イメージングの新展開 超微細構造から細胞機能まで 蛍光イメージングと計測による細胞機能の探索  [通常講演]
    飯村 忠浩
    日本骨代謝学会学術集会プログラム抄録集 2010年07月
  • 生体イメージングの現状と応用 脊椎動物の発生におけるライブイメージング  [通常講演]
    飯村 忠浩
    Cytometry Research 2010年06月
  • 骨成長における概日リズムの可視化  [通常講演]
    中根 綾子, 姫野 彰子, 沼野 利佳, 高木 裕三, 山口 朗, 飯村 忠浩
    日本骨形態計測学会雑誌 2010年05月
  • 蛍光イメージングによる骨細胞の形態・機能分化の計測  [通常講演]
    姫野 彰子, 中根 綾子, 和泉 雄一, 山口 朗, 飯村 忠浩
    日本骨形態計測学会雑誌 2010年05月
  • 顎変形症の発症原因解明の最前線 発生遺伝学から脊椎骨異形成症の責任遺伝子の同定へのプロセス  [通常講演]
    飯村 忠浩
    日本顎変形症学会雑誌 2010年05月
  • 骨のかたちと機能の進化  [招待講演]
    飯村 忠浩
    第16回NPO法人 東京血管疾患研究所セミナー 2009年12月
  • Real time fluorescence imaging in early embryonic body formation  [招待講演]
    飯村 忠浩
    The 26th Naito Conference 2009年10月
  • 蛍光イメージングで探る脊椎動物発生の基盤システム  [招待講演]
    飯村 忠浩
    第1回細胞機能可視化研究会 2009年10月
  • 蛍光イメージングによる骨発生機構の解明  [招待講演]
    飯村 忠浩
    第3回瀬戸内フォーラム 2009年08月
  • 骨の形態的解析法の進歩 骨のin vivo蛍光イメージングの現状と展望  [通常講演]
    飯村 忠浩
    日本骨形態計測学会雑誌 2009年05月
  • Embryonic implications of Hox and the segmentation clock genes for skeletal morphogenesis  [招待講演]
    飯村 忠浩
    第3回 Bone Research Seminar 2009年02月
  • Morphogenetic implications of the segmentation clock and Hox genes in early embryonic spine formation  [招待講演]
    飯村 忠浩
    Tokyo Medical and Dental University Global COE Opening Symposium 2008年09月
  • Regulation and function of Hox genes during chick paraxial mesoderm development  [通常講演]
    飯村 忠浩
    RIKEN CDB セミナー 2008年07月
  • Collinear activation of Hoxb genes during gastrulation controls the timing of mesoderm formation, The 39th Developmemtal Biology Meeting  [招待講演]
    Iimura T, Pourquie O
    The 39th Developmemtal Biology Meeting, Symposium 1:Vertebrate axis formation: Translation of temporal and spatial information 2006年06月
  • Hox遺伝子群による中胚葉形成タイミングの制御  [招待講演]
    飯村 忠浩
    文部科学省科学研究費補助金「特定領域研究」細胞の運命と挙動を支配する細胞外環境のダイナミズム 第1回公開シンポジウム 2006年03月
  • A two-step mechanism is involved in the collinear positioning of Hox gene expression boundaries along the vertebrate skeletal axis  [通常講演]
    Iimura T, Millet S, Malapert P, Dubrulle J, Pourquié O
    44th Annual Midwest Regional Developmental Biology Meeting and Singer Symposium 2004年06月
  • 哺乳類顎顔面の発生におけるBMP-Msx遺伝子カスケードの役割  [通常講演]
    飯村 忠浩
    解剖学雑誌 1999年10月
  • BMPs as a cartilage inducer during mammalian face development.  [通常講演]
    Iimura T, Imai H, Ishiguro K, Ikeda Y, Eto E
    77th General Session & Exhibition of the IADR 1999年03月

その他活動・業績

受賞

  • 2018年07月 日本骨代謝学会 学術賞
     
    受賞者: 飯村 忠浩
  • 2010年09月 歯科基礎医学会 ライオン学術賞
     
    受賞者: 飯村 忠浩
  • 2010年04月 日本歯科骨粗鬆症研究会 優秀演題賞
     
    受賞者: 飯村 忠浩
  • 2008年05月 日本発生生物学会 論文賞
     
    受賞者: 飯村 忠浩
  • 1999年03月 国際歯科研究学会 Hatton Travel Award
     
    受賞者: 飯村 忠浩

共同研究・競争的資金等の研究課題

  • 科学研究費補助金:基盤研究(B)
    研究期間 : 2018年04月 -2021年03月 
    代表者 : 飯村 忠浩
  • 科学研究費補助金:挑戦的研究(萌芽)
    研究期間 : 2018年04月 -2020年03月 
    代表者 : 飯村 忠浩
  • イメージング・シミュレーション・オミクスによる骨格形成機構の多角的解析
    科学研究費補助金:基盤研究(B)
    研究期間 : 2014年04月 -2018年03月 
    代表者 : 飯村 忠浩
  • 3次元蛍光イメージングによる骨細胞機能ダイナミズムの可視化と骨の生理・病態解析
    科学研究費補助金:基盤研究(B)
    研究期間 : 2011年04月 -2014年03月 
    代表者 : 飯村 忠浩
  • 3次元蛍光イメージングによる骨の形態と機能のヘテロジェナイエティの網羅的可視化
    科学研究費補助金:新学術領域研究 (研究領域提案型)
    研究期間 : 2011年04月 -2013年03月 
    代表者 : 飯村 忠浩
  • 脳と骨の蛍光・発光ライブイメージングによる骨時計の発達機構の解明
    科学研究費補助金:挑戦的萌芽研究
    研究期間 : 2011年04月 -2013年03月 
    代表者 : 飯村 忠浩
  • 脳頭蓋および顎顔面頸部の発生・発達におけ4次元蛍光イメージング法の確立
    科学研究費補助金:挑戦的萌芽研究
    研究期間 : 2009年04月 -2010年03月 
    代表者 : 飯村 忠浩
  • 頭蓋顔面骨の発生分化におけるホメオボックス型転写因子の機能解析
    科学研究費補助金:奨励研究(A)
    研究期間 : 1997年04月 -1999年03月 
    代表者 : 飯村 忠浩
  • 骨形成タンパク質(BMP)のシグナル伝達機構に関する分子生物学的研究
    科学研究費補助金:特別研究員奨励費
    研究期間 : 1995年07月 -1997年03月 
    代表者 : 飯村 忠浩
  • 骨形成タンパク質(BMP)の細胞内シグナル伝達機構に関する分子生物学的研究
    科学研究費補助金:特別研究員奨励費
    研究期間 : 1992年04月 -1995年03月 
    代表者 : 飯村 忠浩

教育活動情報

主要な担当授業

  • 発表・論文執筆法演習Ⅰ
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 歯学研究科
    キーワード : 研究計画,文献検索,研究のまとめ,口頭発表,論文作製
  • 発表・論文執筆法演習Ⅰ
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 歯学院
    キーワード : 研究計画,文献検索,研究のまとめ,口頭発表,論文作製
  • 発表・論文執筆法演習Ⅱ
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 歯学研究科
    キーワード : 研究計画,文献検索,研究のまとめ,口頭発表,論文作製
  • 発表・論文執筆法演習Ⅱ
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 歯学院
    キーワード : 研究計画,文献検索,研究のまとめ,口頭発表,論文作製
  • 発表・論文執筆法演習Ⅲ
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 歯学研究科
    キーワード : 研究計画,文献検索,研究のまとめ,口頭発表,論文作製
  • 発表・論文執筆法演習Ⅲ
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 歯学院
    キーワード : 研究計画,文献検索,研究のまとめ,口頭発表,論文作製
  • 細胞分子薬理学
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 歯学院
    キーワード : 薬物、受容体、細胞内情報伝達
  • 麻酔薬生体応答学研究
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 歯学院
    キーワード : 中枢神経作用薬、末梢神経作用薬、麻酔薬、疼痛治療薬
  • 歯学研究概論
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 歯学院
    キーワード : 歯学研究,基本的研究技法,基礎知識
  • 口腔生物学と医学
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 歯学院
    キーワード : feeding behavior, vomiting, conditioned taste aversion (CTA), nausea, GLP-1, bacteriology, immunity, lipoprotein, salivary gland, oncogene, oral cancer, orofacial pain, tumor virus, dental materials, cementum, HIV, matrix cell biology
  • 歯学研究概論
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 歯学研究科
    キーワード : 歯学研究,基本的研究技法,基礎知識
  • 口腔病態解析学
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 歯学院
    キーワード : 臨床歯科薬理学、全身的基礎疾患、薬物相互作用
  • 細胞内情報伝達解析学研究
    開講年度 : 2020年
    課程区分 : 博士後期課程
    開講学部 : 歯学院
    キーワード : 薬物、作用機構、受容体、細胞内情報伝達
  • 薬理学・歯科薬理学Ⅰ
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 歯学部
    キーワード : 薬理学、歯科薬理学
  • アクティブラーニング科目Ⅳ
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 歯学部
    キーワード : 科学的思考,問題発見, 自己解決能力
  • 英語演習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 全学教育
    キーワード : ライフサイエンス、科学論文
  • 関連臨床医学
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 歯学部
    キーワード : 関連臨床医学、耳鼻咽喉科学、精神医学、臨床心理学、眼科、皮膚科、産婦人科
  • 一般教育演習(フレッシュマンセミナー)
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 全学教育
    キーワード : バイオ/ライフサイエンス、ナノテクノロジー、学術論文
  • 健康と社会
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 全学教育
    キーワード : 口腔,血管,リンパ管,炎症,歯周組織,生体防御,常在細菌叢,う蝕(虫歯),歯周病,唾液, 口腔ガン,歯垢バイオフィルム
  • 健康と社会
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 全学教育
    キーワード : 咬む(噛む),咀嚼,健康,心の健康 歯科
  • 薬理学・歯科薬理学実習
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 歯学部
    キーワード : 実習、薬理学、歯科薬理学
  • 薬理学・歯科薬理学Ⅱ
    開講年度 : 2020年
    課程区分 : 学士課程
    開講学部 : 歯学部
    キーワード : 薬理学、歯科薬理学

大学運営

委員歴

  • 2021年 - 現在   日本薬理学会   学術評議員
  • 2020年 - 現在   日本口腔科学会   評議員
  • 2018年 - 現在   骨形態計測学会   ホームページ担当委員
  • 2017年 - 現在   先端歯学国際教育研究ネットワーク   構成委員
  • 2015年 - 現在   口腔医科学フロンティア研究会   世話人
  • 2014年 - 現在   歯科基礎医学会   代議員
  • 2014年 - 現在   日本骨形態計測学会   理事
  • 2014年 - 現在   日本骨代謝学会   教育・復興支援委員
  • 2013年 - 現在   日本骨代謝学会   評議員
  • 2009年 - 現在   日本骨形態計測学会   評議員
  • 2019年 - 2021年   日本顕微鏡学会   理事
  • 2016年 - 2019年   日本顕微鏡学会   関西支部 役員
  • 2011年 - 2015年   骨形態計測学会   学会あり方委員
  • 2009年 - 2014年   歯科基礎医学会   評議員

社会貢献活動

  • 愛媛県立松山東高等学校スーパーグローバルハイスクール事業
    期間 : 2015年04月 - 2016年09月
    役割 : 講師


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