SEARCH

検索詳細

劉　軒宇 (リユウ　ケンウ)

歯学研究院助教

研究者基本情報

■ 学位
  • 博士（歯学）, 国立大学法人北海道大学, 2025年03月
■ URL
researchmap URLホームページURL■ ID 各種
研究者番号
  • 11019069
J-Global ID■ 研究キーワード・分野
研究分野
  • ライフサイエンス, 常態系口腔科学

経歴

■ 経歴
経歴
  • 2025年04月 - 現在
    国立大学法人北海道大学, 大学院歯学研究院, 学術研究員
学歴
  • 2020年04月 - 2025年03月, 北海道大学, 大学院歯学院 博士課程口腔医学専攻
  • 2013年09月 - 2018年06月, 南昌大学, 歯学部, 中華人民共和国

研究活動情報

■ 受賞
  • 2025年05月, 第45回日本骨形態計測学会, 第45回日本骨形態計測学会 若手研究者賞
    アバロパラチドはモデリングによる骨形成を誘導する-骨粗鬆症モデルマウス大腿骨骨幹端の形態学的解析-
    劉 軒宇
■ 論文
  • Histochemical Assessment of Cementum and Alveolar Bone in SDT fa/fa Rat Mimicking Type II Diabetes.
    Tomoka Hasegawa; Mako Sakakibara; Xuanyu Liu; Mai Haraguchi-Kitakamae; Weisong Li; Haoyu Wang; Yan Shi; Jiaxin Cui; Hiromi Hongo; Tomomaya Yamamoto; Miki Abe-Takagi; Haruhi Maruoka; Hirofumi Miyaji; Minqi Li; Norio Amizuka
    Oral diseases, 2025年08月31日, ［査読有り］, ［国際誌］
    英語, 研究論文（学術雑誌）
  • Histochemical assessment of the anabolic effects of abaloparatide on the femoral metaphyses of ovariectomized mice.
    Xuanyu Liu; Tomoka Hasegawa; Mako Sakakibara; Tomomaya Yamamoto; Mai Haraguchi-Kitakamae; Hotaka Ishizu; Yan Shi; Jiaxin Cui; Weisong Li; Wang Haoyu; Hiromi Hongo; Tomohiro Shimizu; Yoichi Ohiro; Norio Amizuka
    Journal of oral biosciences, 67, 2, 100663, 100663, 2025年04月18日, ［査読有り］, ［国際誌］
    英語, 研究論文（学術雑誌）, OBJECTIVE: To clarify the mechanism of bone anabolism induced by the parathyroid hormone-related peptide analog abaloparatide, we histochemically examined the femora of ovariectomized mice treated with abaloparatide. METHODS: Twelve-week-old female C57BL/6J mice underwent ovariectomies (OVX), and were then administered either abaloparatide (30 μg/kg/day: OVX+ABL group) or vehicle (OVX group) via daily intraperitoneal injection. Femora were harvested at 0, 2, 4, and 6 weeks post-administration and subjected to micro-CT imaging, TRAP, cathepsin K, ALP, and PHOSPHO1 staining, along with calcein labeling. RESULTS: In the OVX group, trabecular number and bone volume gradually decreased over time, whereas the OVX + ABL group maintained these values to 6 weeks after OVX. The numbers of TRAP-positive/cathepsin K-reactive osteoclasts per bone surface area were similar between the OVX and OVX + ABL group, except for a temporary increase at 4 weeks in the OVX group. In the OVX group, the areas of ALP-positive osteoblastic cells and PHOSPHO1-reactive mature osteoblasts decreased, whereas in the OVX+ABL group, ALP-positive osteoblastic cells surrounded the trabeculae, and long lines of PHOSPHO1-reactive mature osteoblasts expanded to the terminal region of the trabeculae. In addition, long continuous calcein labeling was seen on slightly convex new bone, indicating modeling-based bone formation in the OVX + ABL group. The bone formation rate/bone surface ratio and the total length of modeling-based bone formation sites were higher in the OVX + ABL group than in the OVX group. CONCLUSION: Abaloparatide suppresses bone loss following ovariectomy by promoting both remodeling-based and modeling-based bone formation.
  • Alendronate inhibits bone-specific blood vessels in the femoral metaphyses of mice.
    Tomoka Hasegawa; Mako Sakakibara; Xuanyu Liu; Hirona Yoshino; Yan Shi; Jiaxin Cui; Mai Haraguchi-Kitakamae; Weisong Li; Wang Haoyu; Tomomaya Yamamoto; Hotaka Ishizu; Tamaki Sekiguchi; Tomohiro Shimizu; Norio Amizuka
    Journal of oral biosciences, 67, 2, 100655, 100655, 2025年03月19日, ［査読有り］, ［国際誌］
    英語, 研究論文（学術雑誌）, To determine whether alendronate affects vascular endothelial cells and regulates the interactions between blood vessels and osteoblasts, we have examined the femoral metaphyses of alendronate-administered mice. Following administration, the bone-specific blood vessels exhibited significantly reduced luminal diameters and rough luminal surfaces with numerous small protrusions and vesicles. Although the osteoclast distribution remained unchanged in ALN-treated mice, osteoblasts were inactivated in the metaphyseal regions where blood vessels had shrunk. Additionally, the expression of genes such as Ephb4/Efnb2, which mediate vascular endothelial cell-osteoblast interactions, was diminished. Therefore, alendronate may primarily affect bone-specific blood vessels, thus leading to osteoblast inactivation.
  • Histochemical assessment of the femora of spontaneously diabetic torii-leprfa (SDT-fa/fa) rats that mimic type II diabetes.
    Qi Yao; Kanako Tsuboi; Hiromi Hongo; Mako Sakakibara; Tomomaya Yamamoto; Mai Haraguchi-Kitakamae; Hotaka Ishizu; Xuanyu Liu; Yan Shi; Weisong Li; Jiaxin Cui; Tomohiro Shimizu; Norio Amizuka; Atsuro Yokoyama; Tomoka Hasegawa; Kiwamu Sakaguchi
    Journal of oral biosciences, 67, 1, 100602, 100602, 2025年03月, ［査読有り］, ［国際誌］
    英語, 研究論文（学術雑誌）, OBJECTIVE: To elucidate the mechanisms underlying diabetic osteoporosis, we conducted a comprehensive histological examination of the femora of Spontaneously Diabetic Torii-Leprfa (SDT-fa/fa) rats, an established model of obesity-related type 2 diabetes. MATERIALS AND METHODS: Femora from 12 30-week-old male SDT-fa/fa rats and age-matched Sprague-Dawley (SD) rats (controls) were used for detailed histochemical analyses, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, tissue nonspecific alkaline phosphatase (ALP), phosphoethanolamine/phosphocholine phosphatase 1 (PHOSPHO1), dentin matrix protein 1 (DMP-1), matrix extracellular phosphoglycoprotein (MEPE), sclerostin, osteocalcin staining, silver impregnation, von Kossa staining, and micro-computed tomography (CT). RESULTS: Micro-CT and hematoxylin-eosin staining demonstrated significantly reduced trabecular bone volume in the femoral metaphyses of SDT-fa/fa rats. Although the number of TRAP-positive osteoclasts per bone surface remained comparable between both groups, SDT-fa/fa rats exhibited reduced areas of ALP-positive and PHOSPHO1-reactive mature osteoblasts/BS. Silver impregnation revealed a well-organized osteocytic lacunar-canalicular system in both groups. However, immunostaining identified aberrant DMP-1 and MEPE expression localized predominantly in the lacunae in SDT-fa/fa rats and in the lacunae and canaliculi of SD rats. Additionally, intense osteocalcin and sclerostin immunoreactivity was detected in osteocytes, along with a higher proportion of osteocalcin-positive osteocytes in SDT-fa/fa rats, distinguishing them from controls. CONCLUSION: SDT-fa/fa rats displayed a significant decline in osteoblastic function and distinctive distribution patterns of osteocyte-derived peptides, suggesting that this diabetic model may manifest alterations in osteoblastic activity and the osteocytic lacunar-canalicular network.
  • Histochemical analysis of osteoclast and osteoblast distributions on hydroxyapatite/collagen bone-like nanocomposite embedded in rat tibiae.
    Mako Sakakibara; Tomoka Hasegawa; Mai Haraguchi-Kitakamae; Yan Shi; Weisong Li; Jiaxin Cui; Xuanyu Liu; Tomomaya Yamamoto; Hiromi Hongo; Norio Amizuka; Yoshiaki Sato; Masanori Kikuchi
    Journal of oral biosciences, 67, 1, 100612, 100612, 2025年03月, ［査読有り］, ［国際誌］
    英語, 研究論文（学術雑誌）, OBJECTIVES: Hydroxyapatite (HAp)/collagen (Col) cylinders with laminated collagen layers were implanted into the tibial diaphysis of rats and examined histochemically to clarify how the orientation of HAp and Col bone-like nanocomposite fibers in HAp/Col blocks affects bone resorption and formation. METHODS: HAp/Col fibers were synthesized and compressed into cylindrical blocks to mimic bone nanostructures. These were implanted into the cortical bone cavities of 10-week-old male Wistar rats with fiber bundles parallel to the tibial surface. The implants were histologically analyzed at 3, 5, 7, 14, and 28 days after implantation. RESULTS: TRAP-positive osteoclasts appeared after 3-5 days in the lateral region of the graft, where the fiber ends were exposed, but not in the bottom region, where the HAp/Col fibers were parallel to the surface. Osteoclasts were observed in both regions by day 14. PHOSPHO1-positive osteoblasts were first detected on day 5, appearing slightly away from the cylinder laterally but directly on the bottom surface. A few osteoblasts contacted the block laterally, whereas many were observed on the new bone tissue at the bottom, between days 7 and 14. Bone formation was induced earlier in the bottom region, whereas lateral resorption was dominant. This suggested the uncoupling of bone resorption and formation in the early postimplantation stages. However, bone remodeling shifted to coupling between osteoclasts and osteoblasts throughout the cylinder by day 28. CONCLUSION: The orientation of HAp/Col fibers in HAp/Col graft materials substantially affected the preferential induction of bone resorption or formation during the early stages of bone regeneration.
  • Histological assessments for anabolic effects in teriparatide/abaloparatide administered rodent models.
    Tomoka Hasegawa; Tomomaya Yamamoto; Mai Haraguchi-Kitakamae; Hiromi Hongo; Yan Shi; Jiaxin Cui; Xuanyu Liu; Qi Yao; Miki Abe; Haruhi Maruoka; Ayako Yokoyama; Tamaki Sekiguchi; Akito Makino; Norio Amizuka
    Journal of bone and mineral metabolism, 43, 1, 46, 56, 2025年01月, ［査読有り］, ［国内誌］
    英語, 研究論文（学術雑誌）, Parathyroid hormone (PTH) is thought to induce remodeling-based bone formation by promoting osteoclastic activity, a process known as cellular coupling. Our research has shown that the frequency of PTH administration affects trabecular number and thickness. High-frequency PTH administration induced remodeling-based bone formation, while less frequent administration induced both remodeling-based and modeling-based bone formation. Additionally, we found that specific bone sites influence whether remodeling-based or modeling-based bone formation is more likely to occur. Additionally, while PTH significantly increases trabecular bone, it also causes cortical porosis. Our research on the femoral diaphysis showed that PTH administration resulted in the invasion of blood vessels and osteoclasts into the cortical bone. Abaloparatide acts similarly to teriparatide through the parathyroid hormone receptor type 1 (PTH1R) but may have a wider anabolic window due to its lesser impact on bone resorption. Our mouse studies with abaloparatide showed similar results to those seen in human patients, with increased preosteoblastic cell populations and wider anabolic windows when compared with teriparatide. Abaloparatide-induced bone formation cannot be explained solely by remodeling-based bone formation, indicating the need for further research into modeling-based bone formation.
  • Regional difference in the distribution of alkaline phosphatase, PHOSPHO1, and calcein labeling in the femoral metaphyseal trabeculae in parathyroid hormone-administered mice.
    Mai Haraguchi-Kitakamae; Yuhi Nakajima; Tomomaya Yamamoto; Hiromi Hongo; Jiaxin Cui; Yan Shi; Xuanyu Liu; Qi Yao; Haruhi Maruoka; Miki Abe; Tamaki Sekiguchi; Ayako Yokoyama; Norio Amizuka; Yasuyuki Sasano; Tomoka Hasegawa
    Journal of oral biosciences, 66, 3, 554, 566, 2024年09月, ［査読有り］, ［国際誌］
    英語, 研究論文（学術雑誌）, OBJECTIVES: This study aimed to elucidate whether the administration of parathyroid hormone (PTH) results in remodeling- or modeling-based bone formation in different regions of the murine femora, and whether the PTH-driven bone formation would facilitate osteoblastic differentiation into osteocytes. METHODS: Six-week-old male C57BL/6J mice were employed to examine the distribution of alkaline phosphatase (ALP), PHOSPHO1, podoplanin, and calcein labeling in two distinct long bone regions: the metaphyseal trabeculae close to the chondro-osseous junction (COJ) and those distant from the COJ in three mouse groups, a control group receiving a vehicle (sham group) and groups receiving hPTH (1-34) twice a day (PTH BID group) or four times a day (PTH QID group) for two weeks. RESULTS: The sham group showed PHOSPHO1-reactive mature osteoblasts localized primarily at the COJ, whereas the PTH BID/QID groups exhibited extended lines of PHOSPHO1-reactive osteoblasts even in regions distant from the COJ. The PTH QID group displayed fragmented calcein labeling in trabeculae close to the COJ, whereas continuous labeling was observed in trabeculae distant from the COJ. Osteoblasts tended to express podoplanin and PHOSPHO1 independently in the close and distant regions of the sham group, while osteoblasts in the PTH-administered groups showed immunoreactivity of podoplanin and PHOSPHO1 together in the close and distant regions. CONCLUSIONS: Administration of PTH may accelerate remodeling-based bone formation in regions close to the COJ while predominantly inducing modeling-based bone formation in distant regions. PTH appeared to simultaneously facilitate osteoblastic bone mineralization and differentiation into osteocytes in both remodeling- and modeling-based bone formation.
  • Immunohistochemical and Morphometric Assessment on the Biological Function and Vascular Endothelial Cells in the Initial Process of Cortical Porosity in Mice With PTH Administration.
    Miki Abe; Tomoka Hasegawa; Hiromi Hongo; Tomomaya Yamamoto; Yan Shi; Jiaxin Cui; Xuanyu Liu; Qi Yao; Hotaka Ishizu; Haruhi Maruoka; Hirona Yoshino; Mai Haraguchi-Kitakamae; Tomohiro Shimizu; Norio Amizuka
    The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 72, 5, 309, 327, 2024年05月, ［査読有り］, ［国際誌］
    英語, 研究論文（学術雑誌）, To clarify the cellular mechanism of cortical porosity induced by intermittent parathyroid hormone (PTH) administration, we examined the femoral cortical bone of mice that received 40 µg/kg/day (four times a day) human PTH (hPTH) (1-34). The PTH-driven cortical porosity initiated from the metaphyseal region and chronologically expanded toward the diaphysis. Alkaline phosphatase (ALP)-positive osteoblasts in the control mice covered the cortical surface, and endomucin-positive blood vessels were distant from these osteoblasts. In PTH-administered mice, endomucin-reactive blood vessels with TRAP-positive penetrated the ALP-positive osteoblast layer, invading the cortical bone. Statistically, the distance between endomucin-positive blood vessels and the cortical bone surface abated after PTH administration. Transmission electron microscopic observation demonstrated that vascular endothelial cells often pass through the flattened osteoblast layer and accompanied osteoclasts in the deep region of the cortical bone. The cell layers covering mature osteoblasts thickened with PTH administration and exhibited ALP, α-smooth muscle actin (αSMA), vascular cell adhesion molecule-1 (VCAM1), and receptor activator of NF-κB ligand (RANKL). Within these cell layers, osteoclasts were found near endomucin-reactive blood vessels. In PTH-administered femora, osteocytes secreted Dkk1, a Wnt inhibitor that affects angiogenesis, and blood vessels exhibited plasmalemma vesicle-associated protein, an angiogenic molecule. In summary, endomucin-positive blood vessels, when accompanied by osteoclasts in the ALP/αSMA/VCAM1/RANKL-reactive osteoblastic cell layers, invade the cortical bone, potentially due to the action of osteocyte-derived molecules such as DKK1.
  • Early gene expression profiles of anabolic and catabolic molecules in murine bone after a single PTH injection.
    Tomomaya Yamamoto; Haruhi Maruoka; Hiromi Hongo; Hirona Yoshino; Mai Haraguchi-Kitakamae; Xuanyu Liu; Qi Yao; Minqi Li; Norio Amizuka; Tomoka Hasegawa
    Journal of oral biosciences, 65, 4, 395, 400, 2023年12月, ［査読有り］, ［国際誌］
    英語, 研究論文（学術雑誌）, The current study examined the gene expression profiles of anabolic and catabolic molecules after a single parathyroid hormone (PTH) injection in mice. No significant changes were observed in alkaline phosphatase area/tissue volume, tartrate-resistant acid phosphatase-positive osteoclasts, or static bone histomorphometry parameters. However, a sudden and significant decrease in Runx2 expression occurred at 1.5 h post-injection followed by immediate elevation, while sclerostin level was initially downregulated but gradually recovered. Meanwhile, Rankl expression initially increased and then returned to baseline. The prolonged elevation of anabolic molecules and transient increase in catabolic molecules may contribute to the anabolic effect of PTH treatment.
■ その他活動・業績
■ 講演・口頭発表等
  • PTH間歇投与マウス大腿骨の各部位における骨形成機序の差異．
    原口-北構真衣; 王 昊昱; 潘 垚澄; 李 偉松; 石 硯; 崔 佳昕; 中井 悠; 松澤 樹; 巫 浩然; Yelidana Yesibulati; 劉 軒宇; 長谷川智香
    日本解剖学会 第71回東北・北海道連合支部学術集会, 口頭発表（一般）
    2025年09月20日 - 2025年09月21日
  • アレンドロネートの投与量の違いによる破骨細胞と骨芽細胞の抑制について
    山本知真也、榊原真子、原口真衣、劉 軒宇、網塚憲生、長谷川智香
    第45回日本骨形態計測学会, 口頭発表（一般）
    2025年06月26日 - 2025年06月28日
  • HAp/Colナノ複合体骨補填材のコラーゲン配列による破骨細胞と骨芽細胞の局在誘導について
    榊原真子、劉 軒宇、李 偉松、王 昊昱、崔 佳昕、原口-北構 真衣、阿部未来、網塚憲生、菊池正紀、長谷川智香
    第45回日本骨形態計測学会, 口頭発表（一般）
    2025年06月26日 - 2025年06月28日
  • アバロパラチドはモデリングによる骨形成を誘導する-骨粗鬆症モデルマウス大腿骨骨幹端の形態学的解析-
    劉 軒宇、石 硯、王 昊昱、李 偉松、原口-北構 真衣、山本知真也、丸岡春日、横山亜矢子、網塚憲生、長谷川智香
    第45回日本骨形態計測学会, 口頭発表（一般）
    2025年06月26日 - 2025年06月28日
  • アバロパラチド投与動物モデルを用いた逐次療法の組織学的評価
    長谷川智香、山本知真也、劉 軒宇、原口真衣、榊原真子、網塚憲生
    第45回日本骨形態計測学会, シンポジウム・ワークショップパネル（指名）
    2025年06月26日 - 2025年06月28日
  • 骨芽細胞系細胞と血管からみた骨組織：骨質との関連性
    網塚憲生、長谷川智香、山本知真也、榊原真子、原口真衣、劉 軒宇
    第45回日本骨形態計測学会, シンポジウム・ワークショップパネル（指名）
    2025年06月26日 - 2025年06月28日
  • 骨芽細胞分化におけるPTHの部位特異的作用について
    崔 佳昕、石 硯、原口真衣、李 偉松、榊原真子、劉 軒宇、本郷裕美、網塚憲生、長谷川智香
    第130回日本解剖学会/第102回日本生理学会/第98回日本薬理学会合同大会, ポスター発表
    2025年03月17日 - 2025年03月19日
  • 胃切除後骨粗鬆症モデルマウスの大腿骨における組織学的検索
    石 硯、崔 佳昕、原口真衣、李 偉松、榊原真子、劉 軒宇、本郷裕美、網塚憲生、長谷川智香
    第130回日本解剖学会/第102回日本生理学会/第98回日本薬理学会合同大会, ポスター発表
    2025年03月17日 - 2025年03月19日
  • アレンドロネートの投与量の違いによる破骨細胞と骨芽細胞の抑制効果における組織学的解析
    山本知真也、崔 佳昕、石 硯、劉 軒宇、北構-原口真衣、本郷裕美、網塚憲生、長谷川智香
    第42回日本骨代謝学会学術集会, ポスター発表
    2024年06月29日 - 2024年07月02日
  • アバロパラチド投与卵巣摘出マウスのRemodeling-based/Modeling based bone formationにおける組織学的検索
    劉 軒宇、姚 斉、石 硯、崔 佳昕、原口-北構 真衣、本郷裕美、網塚憲生、長谷川智香
    第42回日本骨代謝学会学術集会, ポスター発表
    2024年06月29日 - 2024年07月02日
  • アバロパラチド投与卵巣摘出マウスの長管骨における組織化学的検索
    劉 軒宇、姚 斉、石 硯、崔 佳昕、北構-原口真衣、本郷裕美、網塚憲生、長谷川智香
    第36回北海道骨粗鬆症研究会学術集会, 2024年02月17日, 口頭発表（一般）
  • アレンドロネート投与マウスの骨特異的血管における組織化学的検索
    吉野弘菜、崔 佳昕、石 硯、劉 軒宇、本郷裕美、網塚憲生、長谷川智香
    第36回北海道骨粗鬆症研究会学術集会, 2024年02月17日, 口頭発表（一般）