2022年11月, 日本唾液ケア研究会, 唾液関連優秀論文賞　　　　　　　　　　　　　　　
Recovery of atrophic parotid glands in rats fed a liquid diet by switching to a pellet diet
髙橋 茂

Apoptotic cell death during regressive changes in salivary glands: a morphological perspective　　　　　　　　　　　　　　　
Shigeru Takahashi, Akihiro Nezu, Akihiko Tanimura, Chikage Tamura, Kenji Imamachi, Tadasu Sato
Journal of Oral Biosciences, in press, 2025年03月, ［査読有り］, ［招待有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）

ソフトフード摂取が唾液腺に及ぼす影響に関する形態学的解析　　　　　　　　　　　　　　　
髙橋 茂
日本唾液腺学会誌, 64, 50, 56, 2024年12月, ［招待有り］, ［筆頭著者, 最終著者, 責任著者］
日本語

成長期における液状飼料摂取がラット歯根膜およびセメント質に与える影響　　　　　　　　　　　　　　　
中道祥之, 髙橋 茂, 山本恒之, 大廣洋一
北海道歯学雑誌, 45, 40, 49, 2024年09月, ［査読有り］
日本語

Immunohistochemical investigation of nerve distribution in mature parotid and submandibular glands of rats with a liquid diet　　　　　　　　　　　　　　　
Shigeru Takahashi, Chikage Tamura, Yoshiyuki Nakamichi, Kenji Imamachi, Tsuneyuki Yamamoto
Folia Morphologica, 83, 2, 367, 373, 2024年06月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）

Effects of liquid diet intake on nerve growth in salivary glands of growing rats　　　　　　　　　　　　　　　
Takahashi S, Nakamichi Y, Yamamoto T
Folia Morphologica, 82, 3, 551, 557, 2023年09月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）

Morphological variety of capillary ends invading the epiphyseal plate in rat femora using scanning electron microscopy with osmium maceration
Tsuneyuki Yamamoto, Shigeru Takahashi, Tomoka Hasegawa, Hiromi Hongo, Norio Amizuka
Journal of Oral Biosciences, 64, 3, 346, 351, 2022年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: The function of capillary ends at the epiphyseal plate has been actively investigated. However, their morphology is still poorly understood. This study was designed to examine the capillary ends invading the epiphyseal plate three-dimensionally by scanning electron microscopy and discuss the relationship between their morphology and function. METHODS: Distal halves of the femora of eight-week-old male Wistar rats were used. The specimens were divided into two groups for transmission and scanning electron microscopy. For transmission electron microscopy, sagittal ultrathin sections were routinely prepared after the demineralization of the specimens, and the chondro-osseous junction was examined at the epiphyseal plate. For scanning electron microscopy, the specimens were sagittally freeze-cracked, osmium-macerated, and routinely processed. RESULTS: Endothelial cells of capillary ends had fine fenestrations, and hence they were distinguishable from perivascular cells (also known as septoclasts). Based on the outline and the presence or absence of pores, the capillary ends were divided into four types: closed dome, closed spire, porous dome, and porous spire. The two dome types generally occupied more than half of a lacuna, whereas the two spire types generally occupied only a small part of a lacuna. The porous types engulfed cellular remnants, indicative of degraded chondrocytes, via their pores. Some of the spire types penetrated the transverse septum. CONCLUSIONS: The morphological variety of capillary ends reflected their functional variety. Observations suggest that the capillary ends change their morphology dynamically in response to various functions, including the removal of degraded chondrocytes and perforation of transverse septa.

Responses of salivary glands to intake of soft diet
Shigeru Takahashi, Akihiro Nezu, Akihiko Tanimura, Yoshiyuki Nakamichi, Tsuneyuki Yamamoto
Journal of Oral Biosciences, 64, 2, 210, 216, Elsevier BV, 2022年06月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）

液状飼料飼育によるラット口蓋腺発育への影響　　　　　　　　　　　　　　　
竹渕 塁, 髙橋 茂, 八若保孝
北海道歯学雑誌, 41, 1, 38, 45, 2020年09月, ［査読有り］
日本語, 研究論文（学術雑誌）

ラット口蓋腺の加齢変化に関する組織学的研究　　　　　　　　　　　　　　　
谷脇裕人、髙橋 茂、土門卓文、山崎 裕
北海道歯学雑誌, 40, 2, 87, 94, 2020年03月, ［査読有り］
日本語, 研究論文（学術雑誌）

Recovery of atrophic parotid glands in rats fed a liquid diet by switching to a pellet diet　　　　　　　　　　　　　　　
Takahashi S, Takebuchi R, Taniwaki H, Domon T
Archives of Oral Biology, 96, 39, 45, 2018年12月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）

Histological aspect of the effects of soft food on major salivary glands
Takahashi S, Uekita H, Kato T, Yuge F, Takebuchi R, Taniwaki H, Domon T
Hokkaido Journal of Dental Science, 38, S, 34, 39, 北海道歯学会, 2017年09月, ［招待有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, The modern Japanese population favors soft foods, which do not demand extensive mastication. However, daily intake of soft foods is considered to have unfavorable influences on the mind and body. This is especially within the oral maxillofacial region. Consequently, many studies using experimental animals, feed a liquid or powdered diet and indicate that soft foods negatively affect the jaw bones, masseter muscle, and temporomandibular joint. Furthermore, since a report by Hall and Schneyer in 1964, the effects of soft foods on salivary glands have been under investigation. Soft food intake induces atrophic alteration to the parotid glands in adult animals. In these glands, shrinkage, suppression of proliferation, and apoptotic deletion of acinar cells were observed. In growing animals fed soft foods, parotid gland growth is inhibited through the suppression of an increase of acinar cell size and of acinar cell proliferation, but not through apoptosis. These findings support that unfavorable effects on parotid glands are induced by the intake of soft food regardless of growing or mature phases. However, different observations exist between these two phases. Despite accumulated knowledge on parotid glands, the debate whether soft food affects submandibular and sublingual glands remains controversial. It is the case that many studies agree soft food unfavorably affects parotid glands to a greater extent than submandibular and sublingual glands. This article reviews the histological effects of soft food on major salivary glands and introduces recent data from our research group.

Acinar cell response to liquid diet during rats' growth period differs in submandibular and sublingual glands from that in parotid glands
Shigeru Takahashi, Hiroki Uekita, Hiroto Taniwaki, Takanori Domon
TISSUE & CELL, 49, 2, 275, 284, CHURCHILL LIVINGSTONE, 2017年04月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, Continuously feeding a liquid diet to growing rodents strongly inhibits parotid gland growth, due to suppressed growth of acinar cells. This study investigated whether a liquid diet had a similar effect on submandibular and sublingual glands of growing rats. Rats were weaned on day 21 after birth and then fed a pellet diet in the control group and a liquid diet in the experimental group for 0, 1, 2, 4, and 8 weeks. Their submandibular and sublingual glands were excised, weighed, and examined histologically, immunohistochemically (using antibodies to 5'-bromo-2-deoxyuridine and cleaved caspase 3), and ultra structurally. The submandibular glands did not significantly differ between the control and experimental groups at all tested points. Only at Week 8, acinar cell area and 5'-bromo-2-deoxyuridine-labeling index of acinar cells in sublingual glands were significantly lower in the experimental group than in the control group. These results show that a liquid diet during rats' growth period had no effect on acinar cells in their submandibular glands, and only a slight effect on acinar cells in their sublingual glands of growing rats, in contrast to the marked effect of a liquid diet on parotid glands. (c) 2017 Elsevier Ltd. All rights reserved.

Growth of rat parotid glands is inhibited by liquid diet feeding
Shigeru Takahashi, Hiroki Uekita, Tsuyoshi Kato, Kiichiro Inoue, Takanori Domon
TISSUE & CELL, 47, 3, 336, 341, CHURCHILL LIVINGSTONE, 2015年06月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, This study investigated how liquid diet feeding affects the growth of parotid glands. We weaned 21-day-old rats and thereafter fed them a pellet diet (control group) or a liquid diet (experimental group) for 0, 1, 2, 4, or 8 weeks. Their parotid glands were excised, weighed, examined, and tested for 5-bromo-2'-deoxyuridine (BrdU) and cleaved caspase-3 (Casp-3) as markers of proliferation and apoptosis, respectively. Parotid gland weights were consistently smaller in experimental animals than in controls. Morphometrical analysis showed that control group acinar cells increased in area during the experiment, but experimental group acinar cells were almost unchanged. Labeling indices of BrdU in acinar cells in both groups declined during the experiment, but were consistently lower in the experimental group than in controls. Casp-3-positive acinar cells were rare in both groups, which consistently express significantly similar Casp-3 levels. Ultrastructurally, terminal portions of the experimental parotid glands consisted of a few acinar cells that were smaller than those in controls. Control acinar cells showed mitotic figures within short experimental periods, but not in experimental glands. These observations indicate that liquid diet feeding inhibits growth of parotid glands in growing rats through suppression of growth and proliferation of individual acinar cells, but not through apoptosis. (C) 2015 Elsevier Ltd. All rights reserved.

Changes in collagens and chondrocytes in the temporomandibular joint cartilage in growing rats fed a liquid diet
Hiroki Uekita, Shigeru Takahashi, Takanori Domon, Taihiko Yamaguchi
ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER, 202, 78, 87, ELSEVIER GMBH, URBAN & FISCHER VERLAG, 2015年, ［査読有り］
英語, 研究論文（学術雑誌）, The temporomandibular joint (TMJ) of growing rats fed a soft diet is reported to be smaller in size and to have thinner condyle and glenoid fossa cartilage than rats fed a solid diet. The aim of this study was to determine the effect of a soft diet on the collagens and chondrocytes in the growing TMJ cartilage. Forty-eight male Wistar rats were divided into a control group fed a solid diet and an experimental group fed a liquid diet for 1-8 weeks. After the experimental period, the TMJs were harvested and examined histologically, immunohistochemically for collagen types I, II, and X, and with transmission electron microscopy. The condylar cartilage in the experimental rats showed weak immunoreactions for three types of collagens compared with the controls. The ultrastructure had fewer fine collagen fibrils in the experimental rats compared with that of the controls. The glenoid fossa cartilage in the experimental rats showed narrower Alcian blue-positive areas than the control staining. The immunoreactions for three types of collagen in the experimental rats were also weaker than those of the controls. The chondrocytes in the experimental rats appeared dark, had extended thin cytoplasmic processes, and had formed gap junctions, as assessed by transmission electron microscopy. Fewer fine collagen fibrils, but thick bands of collagen fibrils were observed in the glenoid fossa of the experimental cartilage. The results of the present study showed that a liquid diet had deleterious effects on the quality and quantity of collagens and chondrocytes in the TMJ cartilage in growing rats. (c) 2015 Published by Elsevier GmbH.

Effects of a Liquid Diet on the Temporomandibular Joint of Growing Rats
Tsuyoshi Kato, Shigeru Takahashi, Takanori Domon
MEDICAL PRINCIPLES AND PRACTICE, 24, 3, 257, 262, KARGER, 2015年, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: The aim of the present study was to clarify the effects of a liquid diet on the temporomandibular joint (TMJ) in growing rats. Materials and Methods: Twenty-four male Wistar rats were weaned at 21 days and divided into control and experimental groups (12 in each group). Control rats were fed a solid diet and experimental rats were fed a liquid diet from 1 to 8 weeks. After injection with 5-bromo-2'-deoxyuridine (BrdU), the animals were perfused and the heads were removed. Serial coronal sections of the TMJ were stained with hematoxylin and eosin, or BrdU immunohistochemistry was done (12 rats in each group). Three dimensions and the thicknesses of the cartilage layers of the TMJ were measured, and cell proliferation in the TMJ was examined. Results: After 4 weeks, the height and width of the mandibular fossa and the width and length of the mandibular condyle were smaller in the experimental groups than in the control groups. The cartilage layer in these areas was also thinner at 4 weeks. The BrdU levels in the intermediate zone of the mandibular fossa (at 4 weeks) and the mandibular condyle (at 1 and 4 weeks) were lower in the experimental groups than in the controls. Conclusion: These findings suggest that the growth of the mandibular fossa and mandibular condyle of rats was inhibited by the low proliferative activity of intermediate zone cells induced by liquid feeding. (C) 2015 S. Karger AG, Basel

A proposed core curriculum for dental English education in Japan
Omar M. M. Rodis, Edward Barroga, J. Patrick Barron, James Hobbs, Jayanetti A. Jayawardena, Ikuo Kageyama, Bukasa Kalubi, Clive Langham, Yoshizo Matsuka, Yoichiro Miyake, Naoko Seki, Hiroko Oka, Martin Peters, Yo Shibata, Roxana Stegaroiu, Kazuyoshi Suzuki, Shigeru Takahashi, Hironori Tsuchiya, Toshiko Yoshida, Katsuhiko Yoshimoto
BMC MEDICAL EDUCATION, 14, 239, BIOMED CENTRAL LTD, 2014年11月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Globalization of the professions has become a necessity among schools and universities across the world. It has affected the medical and dental professions in terms of curriculum design and student and patient needs. In Japan, where medicine and dentistry are taught mainly in the Japanese language, profession-based courses in English, known as Medical English and Dental English, have been integrated into the existing curriculum among its 83 medical and 29 dental schools. Unfortunately, there is neither a core curriculum nor a model syllabus for these courses.
Methods: This report is based on a survey, two discussion forums, a workshop, and finally, the drafting of a proposed core curriculum for dental English approved by consensus of the participants from each university.
Results: The core curriculum covers the theoretical aspects, including dental English terms and oral pathologies; and practical aspects, including blended learning and dentist-patient communication. It is divided into modules and is recommended to be offered for at least two semesters.
Conclusions: The core curriculum is expected to guide curriculum developers in schools where dental English courses are yet to be offered or are still in their early development. It may also serve as a model curriculum to medical and dental schools in countries in Asia, Europe, Africa, and Central and South America, where English is not the medium of instruction.

唾液腺組織に関連した再生医学研究の進展　　　　　　　　　　　　　　　
髙橋 茂
北海道歯学雑誌, 35, 1, 73, 76, 2014年09月, ［招待有り］, ［筆頭著者, 最終著者, 責任著者］
日本語, 研究論文（学術雑誌）

Immunohistochemical and ultrastructural investigation of acinar cells in submandibular and sublingual glands of rats fed a liquid diet
S. Takahashi, H. Uekita, T. Kato, F. Yuge, N. Ushijima, K. Inoue, T. Domon
TISSUE & CELL, 46, 2, 136, 143, CHURCHILL LIVINGSTONE, 2014年04月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, In atrophic parotid glands induced by liquid diet, acinar cell apoptosis is increased while proliferative activity is reduced. This study aimed to clarify how liquid diet affects submandibular and sublingual glands, including acinar cell apoptosis and proliferation. Seven-week-old male Wistar rats were fed either a liquid (experimental group) or pellet diet (control group) from 3 to 21 days, respectively. Submandibular and sublingual glands were weighed and examined histologically, ultrastructurally, and immunohistochemically using antibodies to cleaved caspase-3 (Casp-3) and 5-bromo-2'-deoxyuridine (BrdU). Weights of submandibular and sublingual gland from the experimental group were not significantly different from controls at any time point. Histological and ultrastructural characteristics of experimental acinar cells in both glands were normal. Acinar cells in control and experimental submandibular glands were positively stained with periodic acid Schiff (PAS) and weakly stained by alcian blue (AB). In control and experimental sublingual glands, mucous acinar cells were PAS-positive and strongly AB-positive. Although Casp-3and BrdU-positive acinar cells were identified in both glands in the experimental group, their labeling indices were not significantly different from controls. In conclusion, liquid diet in rats does not induce atrophic alterations to acinar cells, including apoptosis and proliferative activity in submandibular and sublingual glands. (C) 2014 Elsevier Ltd. All rights reserved.

食習慣および咀嚼習慣が口腔や全身の健康へ与える影響
髙橋 茂
北海道歯学雑誌, 34, 2, 46, 52, 2014年03月, ［招待有り］, ［筆頭著者, 最終著者, 責任著者］
日本語, 研究論文（学術雑誌）

液状食飼育がラット口蓋腺に与える影響に関する組織学的および免疫組織化学的研究　　　　　　　　　　　　　　　
弓削文彦, 髙橋 茂, 土門卓文, 大畑 昇
北海道歯学雑誌, 33, 2, 160, 167, 2013年03月, ［査読有り］
日本語, 研究論文（学術雑誌）

Involvement of apoptosis and proliferation of acinar cells in atrophy of rat parotid glands induced by liquid diet
Shigeru Takahashi, Hiroki Uekita, Tsuyoshi Kato, Fumihiko Yuge, Natsumi Ushijima, Kiichiro Inoue, Takanori Domon
JOURNAL OF MOLECULAR HISTOLOGY, 43, 6, 761, 766, SPRINGER, 2012年12月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, Parotid glands of experimental animals fed a liquid diet are reported to show atrophy (Hall and Schneyer 1964; Wilborn and Schneyer 1970; Hand and Ho 1981; Scott et al. 1990; Scott and Gunn 1991). To clarify whether apoptosis and proliferation of acinar cells participate in atrophy of rat parotid glands induced by liquid diet, rats were fed a liquid diet and compared to pellet-fed controls. Parotid glands were removed at 3, 7, 14 or 21 days, weighed, and examined using transmission electron microscopy (TEM), and studied immunohistochemically for cleaved-caspase-3 (Casp-3), a marker of apoptotic cells, and 5-bromo-2'-deoxyuridine (BrdU), a marker for proliferating cells. Body weights of experimental rats fed liquid diets were not significantly different from controls fed pellet diets; however weights of experimental parotid glands were smaller than those of controls. In the experimental parotid glands, structures like apoptotic bodies were histologically observed in acini at each time point; more Casp-3-positive acinar cells were identified in experimental parotid glands than in the controls on days 3, 7, and 14. Experimental glands showed fewer BrdU-positive acinar cells at each time point. TEM confirmed typical apoptotic acinar cells in the atrophic glands. These findings suggest that increased acinar cell apoptosis and reduced acinar cell proliferation occur in atrophic parotid glands of rats fed a liquid diet.

北海道大学全学教育科目「唾液のサイエンス」におけるクリッカー使用とその効果の検討　　　　　　　　　　　　　　　
髙橋 茂, 井上貴一朗, 舩橋 誠, 土門卓文
北海道歯学雑誌, 31, 2, 75, 81, 2010年12月, ［査読有り］, ［筆頭著者, 責任著者］
日本語, 研究論文（学術雑誌）

エナメル質研究の忘れ物　　　　　　　　　　　　　　　
脇田 稔, 山本恒之, 土門卓文, 髙橋 茂, 花泉好訓
エナメル質ー形成、構造、遺伝、再生、起源と進化ー（わかば出版）, 5, 13, 2009年07月
日本語, 研究論文（その他学術会議資料等）

Hertwig's epithelial root sheath cells do not transform into cementoblasts in rat molar cementogenesis
Tsuneyuki Yamamoto, Shigeru Takahashi
ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER, 191, 6, 547, 555, ELSEVIER GMBH, URBAN & FISCHER VERLAG, 2009年, ［査読有り］, ［最終著者］
英語, 研究論文（学術雑誌）, It is generally accepted that cementoblasts originate in the process of differentiation of the mesenchymal. cells of the dental follicle. Recently, a different hypothesis for the origin of cementoblasts has been proposed. Hertwig's epithelial root sheath cells undergo the epithelial-mesenchymal transformation to differentiate into cementoblasts. To elucidate whether the epithelial-mesenchymal transformation occurs in the epithelial, sheath, developing rat molars were examined by keratin-vimentin and Runx2 (runt-related transcription factor 2)-keratin double immunostaining. In both acellular and cellular cementogenesis, epithelial sheath and epithelial cells derived from the epithelial. sheath expressed keratin, but did not express vimentin or Runx2. Dental follicle cells and cementoblasts, however, expressed vimentin and Runx2, but did not express keratin. No cells showed coexisting keratin-vimentin or Runx2-keratin staining. These findings suggest that there is no intermediate phenotype transforming epithelial, to mesenchymal. cells, and that epithelial sheath cells do not generate mineralized tissue. This study concludes that the epithelial-mesenchymal transformation does not occur in Hertwig's epithelial. root sheath in rat acellular or cellular cementogenesis and that the dental follicle is the origin of cementoblasts, as has been proposed in the original hypothesis. (C) 2009 Elsevier GmbH. All rights reserved.

Cellular expression of Bcl-2 and Bax in atrophic submandibular glands of rats
Shigeru Takahashi, Yoshitaka Yoshimura, Tsuneyuki Yamamoto, Minoru Wakita
INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, 89, 5, 303, 308, WILEY-BLACKWELL, 2008年10月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, In submandibular gland atrophy, most acinar cells disappear by apoptosis, while many duct cells remain. The present study aimed to establish whether Bcl-2 and Bax, members of the Bcl-2 gene family, regulating the signalling pathway of apoptosis were involved in duct cell survival and acinar cell death in atrophic submandibular glands. The excretory duct of rat submandibular gland was doubly ligated with metal clips from 1 to 14 days to induce atrophy to the gland. The expressions of Bcl-2 and Bax in the atrophic submandibular gland were examined using immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). Immunohistochemically, Bcl-2 expression was identified in duct cells in the experimental glands at all time points. Some acinar cells showed Bax positivity 1 day after excretory duct ligation, and there were more Bax-positive acinar cells on days 3 and 5 when many apoptotic acinar cells were observed. Analysis by RT-PCR showed that the expression of mRNA for Bcl-2 became stronger as the glandular atrophy progressed and that Bax mRNA strongly expressed on days 1 and 3. These observations suggest that Bcl-2 inhibits duct cell apoptosis and Bax promotes apoptosis of acinar cells during atrophy of submandibular glands.

A histological and immunohistochemical study of acellular cementogenesis in rat incisors　　　　　　　　　　　　　　　
Anjuman K.A.Y, Yamamoto T, Takahashi S, Wakita M
Hokkaido Journal of Dental Science, 28, 1, 41, 51, 2007年06月, ［査読有り］
英語, 研究論文（学術雑誌）

Mineralization process during acellular cementogenesis in rat molars: a histochemical and immunohistochemical study using fresh-frozen sections
Tsuneyuki Yamamoto, Takanori Domon, Shigeru Takahashi, Khan Ara Yasmin Anjuman, Chifumi Fukushima, Minoru Wakita
HISTOCHEMISTRY AND CELL BIOLOGY, 127, 3, 303, 311, SPRINGER, 2007年03月, ［査読有り］
英語, 研究論文（学術雑誌）, This study was designed to detect tissue non-specific alkaline phosphatase (TNSALP) by Azo-dye staining, calcium by glyoxal bis (2-hydroxyanil) (GBHA) staining, bone sialoprotein (BSP) and osteopontin (OPN) by immunoperoxidase staining in developing rat molars, and also to discuss the mineralization process during acellular cementogenesis. To restrain a reduction in histochemical and immunohistochemical reactions, fresh-frozen undemineralized sections were prepared. Where the epithelial sheath was intact, TNSALP reaction was observed in the dental follicle, but not in the epithelial sheath. With the onset of dentin mineralization, the BSP- and OPN-immunoreactive, initial cementum layer appeared. At this point, cementoblasts had shown intense TNSALP reaction and GBHA reactive particles (=calcium-GBHA complex) appeared on the root surface. With further development, the reaction of TNSALP and GBHA became weak on the root surface. Previous studies have shown that the initial cementum is fibril-poor and that matrix vesicles and calciferous spherules appear on the root surface only during the initial cementogenesis. The findings mentioned above suggest that: during the initial cementogenesis, cementoblasts release matrix vesicles which result in calciferous spherules, corresponding to the GBHA reactive particles. The calciferous spherules trigger the mineralization of the initial cementum. After principal fiber attachment, mineralization advances along collagen fibrils without matrix vesicles.

Participation of the Fas and Fas ligand systems in apoptosis during atrophy of the rat submandibular glands
Shigeru Takahashi, Glenda C. Gobe, Yoshitaka Yoshimura, Takao Kohgo, Tsuneyuki Yamamoto, Minoru Wakita
INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, 88, 1, 9, 17, BLACKWELL PUBLISHING, 2007年02月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, Most acinar cells and some duct cells undergo apoptosis during atrophy of the submandibular gland. The present study was designed to elucidate whether Fas and its receptor ligand (FasL) are involved during apoptotic atrophy of the gland. The excretory duct of the right submandibular gland of rats was doubly ligated with metal clips from 1 to 14 days for induction of gland atrophy. Control rats were untreated. Fas and FasL expression in the atrophied submandibular gland was detected using immunohistochemistry (IHC) and Western immunoblot. Expression of activated caspase 8 and activated caspase 3 was also detected with IHC. Fas-positive acinar and duct cells and FasL-positive duct cells increased in the atrophic glands at 3 and 5 days after duct ligation when apoptotic cells were commonly observed. Thereafter, Fas- and FasL-positive cells declined in number. Patterns of expression of Fas and FasL using Western immunoblots concurred with the IHC results. Activated caspase 8-positive cells were present at every time interval but peaked at 3 and 5 days following duct ligation. The cells showing immunoreaction for activated caspase 3 first appeared on day 3, with the peak in apoptosis, after which they decreased. The results indicate that the Fas/FasL systems likely play an important role in apoptotic pathways during atrophy of the submandibular gland.

Features of the clear zone of odontoclasts in the Chinook salmon (Oncorhynchus tshawytscha)
T Domon, Y Taniguchi, A Fukui, R Suzuki, S Takahashi, T Yamamoto, M Wakita
ANATOMY AND EMBRYOLOGY, 211, 2, 87, 93, SPRINGER, 2006年03月, ［査読有り］
英語, 研究論文（学術雑誌）, This study aims to clarify the features of the clear zone of odontoclasts on shedding teeth of a teleost fish, Chinook salmon, Oncorhynchus tshawytscha (Walbaum), using a light microscope to determine the orientation between a cell body and a resorptive lacuna, followed by transmission electron microscopy. Ultrathin sections of LR White embedded material were incubated in rabbit anti-actin polyclonal antibody and then were incubated with 15 nm gold-conjugated goat anti-rabbit IgG. The clear zones of odontoclasts showed a variable structure with electron-dense structures on sections, but distinct clear zones were not always seen on odontoclasts. In odontoclasts sectioned in the direction perpendicularly to the surface of a resorptive lacuna, some cells showed a wide clear zone, but two types of clear zones were usually observed: a part composed of some cytoplasmic processes and one composed of several complicatedly interwoven processes. Gold particles were localized on the clear zones, especially in electron-dense structures; very few gold particles were detected in ruffled borders. These results show that the clear zone of odontoclasts in Chinook salmon contains actin. Our results suggest that the clear zone of an odontoclast in Chinook salmon is not always a wide annular structure.

Determination of two different types of cellular cementogenesis in rat molars: A histological and immunohistochemical study
T Yamamoto, T Domon, S Takahashi, AKS Arambawatta, KAY Anjuman, C Fukushima, M Wakita
MATRIX BIOLOGY, 24, 4, 295, 305, ELSEVIER SCIENCE BV, 2005年06月, ［査読有り］
英語, 研究論文（学術雑誌）, To elucidate the attachment mechanism of dentin and cellular cementum, developing and developed cellular cementum of rat molars was examined by light microscopy. Routine histological staining, immunohistochemical staining for bone sialoprotein (BSP) and osteopontin (OPN), and digestion tests with trypsin were conducted. Two different types of cellular cementogenesis were established, one on the mesial (type I cementogenesis) and one on the distal sides (type 11 cementogenesis) of the examined roots. In the type I cementogenesis a thin initial cementum layer, which was fibril-poor, hematoxylin-stained, and immunopositive for BSP and OPN, appeared on the mineralized dentin. With cellular cementogenesis, the layer became the cemento-dentinal junction. The cementum mineralization did not precede the dentin mineralization. After trypsin treatment the cemento-dentinal junction lost immunoreactivity, for BSP and OPN and the cementum was detached from the dentin. In the type 11 cementogenesis the cellular cementum formed directly on the predentin without the initial cementum layer and the cementum mineralization preceded the dentin mineralization. Cemental and predentinal fibrils appeared to intermingle, as the cemento-dentinal junction was indiscernible by any staining. Trypsin treatment did not cause cementum detachment. The findings of the present study suggest that: (1) The type I cementogenesis requires the intervening initial cementum to bind cementum and dentin and to induce the cementum mineralization. (2) In the type 11 cementogenesis the cemento-dentinal attachment depends on fibril intermingling and the cementum mineralization advances apically and very rapidly, probably producing mineralization foci. (3) The formation of the initial cementum depends on the speed of the cementogenesis in the apical direction. (c) 2005 Elsevier B.V/International Society of Matrix Biology. All rights reserved.

Biological behavior of myoepithelial cells in the regeneration of rat atrophied sublingual glands following release from duct ligation
S Takahashi, T Kohgo, S Nakamura, A Arambawatta, T Domon, T Yamamoto, M Wakita
JOURNAL OF MOLECULAR HISTOLOGY, 36, 5, 373, 379, SPRINGER, 2005年06月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, The present study aimed to clarify how myoepithelial cells behave during regeneration of an atrophied sublingual gland by investigating cell proliferation and ultrastructure. Atrophy of rat sublingual glands was induced by unilateral ligation of the excretory duct near the hilum with metal clips, which were then removed after one week of ligation for regeneration. The sublingual glands 0-14 days after unligation were examined with single immunohistochemistry for actin as a marker of myoepithelial cells, double immunohistochemistry for actin and proliferating cell nuclear antigen (PCNA) as a marker of proliferating cells, and transmission electron microscopy (TEM). The single immunohistochemistry and TEM showed that myoepithelial cells surrounded residual ducts in the atrophied glands and immature and mature acini in the regenerating glands. Although PCNA-positive myoepithelial cells were identified during regeneration, PCNA labeling indices of myoepithelial cells were low at all time points except at day 7. Ultrastructurally, myoepithelial cells showing bizarre shaped structures in the atrophy changed with maturation of differentiating acinar cells and appeared normal in the regenerated glands. There was no differentiation of the remaining duct cells to myoepithelial cells. These observations suggest that proliferation of myoepithelial cells and differentiation to myoepithelial cells do not commonly participate in the regeneration of atrophied sublingual glands and that the bizarre shaped myoepithelial cells in the atrophied sublingual glands recover the original shapes with acinar cell regeneration.

Active participation of apoptosis and mitosis in sublingual gland regeneration of the rat following release from duct ligation
S Takahashi, S Nakamura, T Domon, T Yamamoto, M Wakita
JOURNAL OF MOLECULAR HISTOLOGY, 36, 3, 199, 205, SPRINGER, 2005年03月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, This study was designed to establish how mitotic cell proliferation and apoptotic cell death participate in the regeneration of atrophied rat sublingual glands. To induce atrophy to the sublingual gland of rats, the excretory duct was ligated unilaterally near the hilum, and after 1 week of ligation (day 0) the duct ligation was released to enable gland regeneration. The regenerating glands were examined with routine histology, immunohistochemistry for proliferating cell nuclear antigen (PCNA) as a marker of proliferating cells, terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) as a marker of apoptotic cells, and transmission electron microscopy. At day 0, a few acini and many ducts remained in the atrophic sublingual glands, and newly formed immature acini were observed at day 3. Thereafter acinar cells progressively matured and increased in number, although the number of ducts decreased. Many PCNA- and some TUNEL-positive cells were seen in acini and ducts during regeneration. The labeling indices for both cell types were statistically significantly different from that of the control at several time points of the regeneration. Apoptotic and mitotic cells were also confirmed to be present in the experimental sublingual glands by electron microscopy. These observations suggest that apoptosis as well as mitosis of duct and acinar cells actively participate in and play important roles in sublingual gland regeneration.

Odontoclasts in the Chinook salmon differ from mammalian odontoclasts by exhibiting a great proportion of cells with high nuclei number
T Domon, A Fukui, Y Taniguchi, R Suzuki, S Takahashi, T Yamamoto, M Wakita
ANATOMY AND EMBRYOLOGY, 209, 2, 119, 128, SPRINGER, 2004年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Odontoclasts resorbing teeth are multinucleated cells. Previously, the authors have investigated the distribution of number of nuclei per human odontoclast and showed that the mean number of nuclei per cell is 5.3, the median is 4, and 93.8% of cells have 10 or fewer nuclei. Teleost odontoclasts have features similar to those of mammals; however, the distribution of number of nuclei per cell remains unknown. The present study aimed to examine the distribution of number of nuclei per odontoclast in a teleost fish, Chinook salmon, Oncorhynchus tshawytscha (Walbaum), and to clarify the difference of number of nuclei in odontoclasts between Chinook salmon and humans. The maxillae and mandibles of Chinook salmon were fixed, decalcified, and embedded in Epon 812. Specimens were serially sectioned into 0.5-mum semithin sections and examined by light microscopy. Cells possessing a brush border adjacent to a resorptive lacuna were identified as odontoclasts, and 246 odontoclasts were investigated to determine the distribution of nuclei per cell. The mean number of nuclei per cell was 21.8 and the median was 17; only 24.4% of odontoclasts had 10 or fewer nuclei, and 95.5% had 50 or fewer nuclei. These results suggest that the range for the number of nuclei per odontoclast in Chinook salmon is greater than that in humans.

Acinar cell differentiation during regeneration of atrophied sublingual glands of rats following release from duct ligation
Takahashi S, Arambawatta A.K.S, Domon T, Yamamoto T, Wakita M
Hokkaido Journal of Dental Science, 25, 2, 322, 329, 2004年12月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）

Immunolocalization of proteoglycans and bone-related noncollagenous glycoproteins in developing acellular cementum of rat molars
T Yamamoto, T Domon, S Takahashi, AKS Arambawatta, M Wakita
CELL AND TISSUE RESEARCH, 317, 3, 299, 312, SPRINGER, 2004年09月, ［査読有り］
英語, 研究論文（学術雑誌）, To elucidate the roles of proteoglycans (PGs), bone sialoprotein (BSP), and osteopontin (OPN) in cementogenesis, their distribution was investigated in developing and established acellular cementum of rat molars by an immunoperoxidase method. To characterize PGs, antibodies against five species of glycosaminoglycans (GAGs), chondroitin-4-sulfate (C4S), chondroitin-6-sulfate (C6S), unsulfated chondroitin (C0S), dermatan sulfate (DS), and keratan sulfate (KS) were used. Routine histological staining was also applied. With onset of dentin mineralization, the initial cementum appeared on the dentin surface as a hematoxylin-stained fibril-poor layer. Subsequently, primitive principal fibers attached to the initial cementum. As the acellular cementum containing extrinsic fibers covered the initial cementum, the initial cementum formed the cemento-dentinal junction. Following immunohistochemistry at the earliest time of cementogenesis, the initial cementum was intensely immunoreactive for C4S, C6S, C0S, BSP, and OPN. After the initial cementum was embedded, neither the cemento-dentinal junction nor the cementum was immunoreactive for any GAG species. However, the cementum and cemento-dentinal junction were consistently immunoreactive for BSP. Although the cemento-dentinal junction was consistently immunoreactive for OPN, the remaining cementum showed no significant immunoreactivity. Thus, initial acellular cementogenesis requires a dense accumulation of PGs, BSP, and OPN, which may be associated with the mineralization process independently of collagen fibrils and initial principal fiber attachment.

Mitotic proliferation of myoepithelial cells during regeneration of atrophied rat submandibular glands after duct ligation
S Takahashi, K Shinzato, T Domon, T Yamamoto, M Wakita
JOURNAL OF ORAL PATHOLOGY & MEDICINE, 33, 7, 430, 434, BLACKWELL MUNKSGAARD, 2004年08月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, BACKGROUND: The purpose of the present study was to elucidate whether myoepithelial cells proliferate mitotically during regeneration of rat submandibular glands after atrophy.
METHODS: The excretory duct of the right submandibular gland of rats was doubly ligated near the hilum with metal clips, which were removed after 7 days of ligation (day 0). The regenerating right submandibular glands were removed from 0 to 14 days after removal of the clips. The removed tissue was examined with immunohistochemical double staining for proliferating cell nuclear antigen (PCNA) as a marker of proliferating cells and actin as a marker of myoepithelial cells, as well as with transmission electron microscopy (TEM).
RESULTS: The PCNA-positive myoepithelial cells were observed at the periphery of transitional duct-acinar structures, ducts and acini in the regenerating glands at every time-point, and the PCNA-labeling index of myoepithelial cells increased greatly especially between day 2 and 4. The mitosis of myoepithelial cell was also identified by TEM at day 4.
CONCLUSION: These findings suggest that myoepithelial cells are able to proliferate mitotically during regeneration of rat submandibular gland.

Prenatal development of the palatine gland of rats
K Shinzato, S Takahashi, A Wakita, M Morita
TISSUE & CELL, 36, 2, 115, 120, CHURCHILL LIVINGSTONE, 2004年04月, ［査読有り］
英語, 研究論文（学術雑誌）, The present study aimed to elucidate the prenatal development of the rat palatine gland. Parasagittal 5 mum thick serial sections made from Wistar rats at embryonic days (E) 17 to 22 were stained with haematoxylin-eosin (HE), Alcian blue-Kernechtrot or immunohistochemistry for 5-bromo-2-deoxyuridine (BrdU) as a marker of proliferating cells. Additionally, three-dimensional images of developing glandular parenchyma were reconstructed from serial HE sections with a personal computer. At E 17, several thickenings of the palatal epithelium had appeared which thereafter became the epithelial cords. Branching and lumenization commenced at E 20, and immature acini were observed at E 21. Three-dimensional reconstruction showed that the proximal part of the epithelial cord differentiated into the duct, and the distal part of the epithelial cord differentiated into the acinus. In immunohistochemical staining, there were many BrdU-positive cells in the epithelial cords including thickenings of the palatal epithelium, ducts, and acini. The BrdU labeling index of the cells of the epithelial cord was the highest (statistically significant) of the three in the primitive palatine gland. In conclusion, during the development of the rat Palatine gland, epithelial cords with very high proliferative activity arise from the palatal epithelium, and then the proximal part of the epithelial cord differentiates into the duct, and the distal part of the epithelial cord differentiates into the acinus. Proliferation of these glandular parenchyma contributes to the growth of the developing palatine gland. (C) 2003 Elsevier Ltd. All rights reserved.

[Serial review No.8. Dental embryology: microstructural formation of teeth].
Wakita M, Yamamoto T, Domon T, Takahashi S
Clinical calcium, 14, 195, 198, 1, 2004年01月, ［査読有り］

歯の微細構造　　　　　　　　　　　　　　　
脇田 稔, 山本恒之, 土門卓文, 髙橋 茂
Clinical Calcium, 14, 1, 195, 198, 2004年01月, ［招待有り］, ［最終著者］
日本語, 研究論文（その他学術会議資料等）

Cell death and cell proliferation in the regeneration of atrophied rat submandibular glands after duct ligation
S Takahashi, K Shinzato, S Nakamura, T Domon, T Yamamoto, M Wakita
JOURNAL OF ORAL PATHOLOGY & MEDICINE, 33, 1, 23, 29, BLACKWELL MUNKSGAARD, 2004年01月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, BACKGROUND: The present study aimed to clarify the proliferation and apoptosis of parenchymal cells during regeneration of rat submandibular glands following atrophy.
METHODS: Atrophy of the right submandibular gland of rats was induced by excretory duct ligation at the hilum with metal clips, which were removed 1 week (day 0) after ligation. The right submandibular glands were collected from 0 to 14 days after removal of the clips and investigated using immunohistochemistry for proliferating cell nuclear antigen (PCNA) as a marker of proliferating cells, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) as a marker of apoptotic cells, and transmission electron microscopy (TEM).
RESULTS: After 1 week of ligation, there were many remaining ducts and a few acini in the atrophic glands. At day 3 after discontinuing the ligation, newly formed acini appeared and thereafter increased in number and maturity. Many residual and newly formed acinar cells showed positive reaction to PCNA especially at days 4 and 5. The PCNA-positive duct cells decreased in number with the regeneration. A few TUNEL-positive acinar and duct cells were identified during regeneration. Mitosis and apoptosis of parenchymal cells were also identified by TEM.
CONCLUSIONS: During regeneration of the submandibular gland after atrophy, both residual and newly formed acinar cells proliferate actively. There is also apoptosis of parenchymal cells; however, the significance of apoptosis is low.

A crown reconstructing method for resin-embedded transparent teeth
T Yamamoto, T Domon, S Takahashi, MN Islam, M Wakita
QUINTESSENCE INTERNATIONAL, 34, 10, 749, 751, QUINTESSENCE PUBL CO INC, 2003年11月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: Resin-embedded transparent teeth are devoid of the original crown morphology, because enamel is lost by demineralization. This study was designed to reproduce artificial enamel and to reconstruct the original crown morphology for resin-embedded transparent teeth. Method and materials: The impression of the coronal portion of human permanent teeth was taken with a silicone impression material. After demineralization, drawing ink was injected into the pulp cavities. The ink-infiltrated teeth were made transparent with methyl salicylate and embedded with polyester resin. Urethane prepolymer was injected into the impression, and the resin-embedded teeth were reinserted into the impression. After polymerization of the urethane resin, the specimens and the urethane resin were removed from the impression. Results: The original crown morphology of the resin-embedded transparent teeth could be precisely reconstructed with artificial and removable enamel. The resin-embedded teeth showed morphologic details of the black-stained pulp cavities through the transparent dentin and cementum. Conclusion: This study established a crown reconstructing method for resin-embedded transparent teeth. The specimens will be useful for demonstration of morphology of teeth and pulp cavities.

Proliferation and distribution of myoepithelial cells during atrophy of the rat sublingual gland
S Takahashi, K Shinzato, T Domon, T Yamamoto, M Wakita
JOURNAL OF ORAL PATHOLOGY & MEDICINE, 32, 2, 90, 94, BLACKWELL MUNKSGAARD, 2003年02月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, Background: The present study was aimed to determine the proliferation and distribution of myoepithelial cells during atrophy of rat sublingual glands.
Methods: The excretory duct of the right sublingual gland of rats was doubly ligated with metal clips to induce atrophy in the gland. The atrophic sublingual glands were taken from 1 to 28 days after duct ligation and examined with single immunohistochemistry for actin as a marker of myoepithelial cells and with immunohistochemical double staining for actin and proliferating cell nuclear antigen (PCNA) as a marker of proliferating cells.
Results: In unligated sublingual glands, myoepithelial cells embraced acini and intercalated ducts, but not striated and interlobular excretory ducts. In the early stages of atrophy, myoepithelial cells surrounded small ducts but not large ones. However, in the later stages of atrophy, myoepithelial cells were also observed at the periphery of the large ducts. The immunohistochemical double staining showed that there were PCNA-positive myoepithelial cells in the normal as well as in the atrophic sublingual glands. However, the PCNA labeling indices of myoepithelial cells were low in the unligated and atrophic sublingual glands, and there were no statistically significant differences in these labeling indices.
Conclusion: The observations suggest that the distribution of myoepithelial cells change during atrophy of rat sublingual glands and that myoepithelial cells have low proliferative activity in both the normal and atrophic condition of rat sublingual glands.

唾液腺筋上皮細胞は分裂増殖するのだろうか？　　　　　　　　　　　　　　　
髙橋 茂
北海道歯学雑誌, 24, 77, 79, 2003年, ［招待有り］, ［筆頭著者, 最終著者, 責任著者］
日本語, 研究論文（学術雑誌）

The roles of apoptosis and mitosis in atrophy of the rat sublingual gland
S Takahashi, K Shinzato, S Nakamura, T Domon, T Yamamoto, M Wakita
TISSUE & CELL, 34, 5, 297, 304, CHURCHILL LIVINGSTONE, 2002年10月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, The roles of apoptosis and mitosis of acinar and duct cells in the atrophy of the sublingual gland of rat induced by double duct ligation was investigated using immunohistochemistry for proliferating cell nuclear antigen (PCNA), terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling (TUNEL), and transmission electron microscopy (TEM). Many PCNA-positive duct cells were observed 3 days after duct ligation, and the numbers decreased thereafter. At 3 and 5 days, several TUNEL-positive acinar cells were observed and typical apoptotic acinar cells were identified by TEM. Necrotic acinar cells were also observed ultrastructurally. After 7 days, there were few acini but many ducts, as well as many structures representing transition from acinus to duct. These observations demonstrate that acinar cell loss by apoptosis and duct cell proliferation by mitosis occur in atrophic sublingual glands as well as in other atrophic salivary glands. In addition, it appears that the transition from acinar to duct cell and the necrosis of acinar cells play important roles in the atrophy of the sublingual gland. (C) 2002 Elsevier Science Ltd. All rights reserved.

Three-dimensional distribution of the clear zone of migrating osteoclasts on dentin slices in vitro
T Domon, Y Yamazaki, A Fukui, Y Ohnishi, S Takahashi, T Yamamoto, M Wakita
TISSUE & CELL, 34, 5, 326, 336, CHURCHILL LIVINGSTONE, 2002年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Osteoclasts are cells that dynamically alternate resorption and migration on bone surfaces, and have the special structure called ruffled borders and clear zones by transmission electron microscopy (TEM). However, TEM features, especially the distribution of the clear zone of osteoclasts during migration, remains unclear. This study aimed to examine osteoclasts cultured on dentin slices by TEM and clarify the features of migrating osteoclasts, especially the three-dimensional distribution of clear zones. Osteoclasts obtained from mice were cultured with dentin slices for 72 h, and then cells were fixed and the tartrate-resistant acid phosphatase (TRAP) activity was detected. Specimens were embedded in Epon, then TRAP-positive cells were serially sectioned by alternating semithin and ultrathin sections. The cells were examined by TEM and the three-dimensional structures were reconstructed by computer. By TEM, most TRAP-positive cells were resorbing osteoclasts with ruffled borders and a clear zone. There were osteoclasts without ruffled borders, and these cells had clear zone-like structures and lamellipodia. The three-dimensional reconstruction showed that resorbing osteoclasts had rounded contours and ring-shaped clear zones encircling ruffled borders, and that osteoclasts without ruffled borders had irregular and flat shapes; the clear zone-like structures showed a dot or patch-like distribution. The presence of lamellipodia of the osteoclasts without ruffled borders shows that the cells are migrating osteoclasts. These results suggest that dot or patch-like distribution is the feature of the clear zone of osteoclasts during migration, and that these structures play the role of focal contacts and adhesion to the dentin surfaces during cell migration. (C) 2002 Published by Elsevier Science Ltd.

Ultrastructural study of cell-cell interaction between osteoclasts and osteoblasts/stroma cells in vitro
T Domon, Y Yamazaki, A Fukui, Y Ohnishi, S Takahashi, T Yamamoto, M Wakita
ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER, 184, 3, 221, 227, URBAN & FISCHER VERLAG, 2002年05月, ［査読有り］
英語, 研究論文（学術雑誌）, Many biochemical reports support cell-cell interaction between osteoclasts and osteoblasts/stroma cells in vitro, however there have been few morphological studies supporting this. Details of cell-cell interaction between osteoclasts and osteoblasts/stroma cells remain unclear. The present study examined cell-cell interaction between osteoclasts and osteoblasts/stroma cells by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Osteoclasts, osteoblasts/stroma cells, and bone marrow cells obtained from 10-day-old ddY mice were cultured on dentin slices for 72 hr. Specimens were fixed, and some were examined by SEM. Specimens were decalcified, embedded in Epon after determination of the tartrate-resistant acid phosphatase activity (TRAP), and TRAP-positive cells for investigation were serially sectioned by alternating semithin and ultrathin sections., and then examined by TEM. By SEM, many cellular contacts were seen between the cells cultured on the dentin, but by TEM there were few special structures on the cell membranes between osteoclasts and osteoblasts/stroma cells, or between osteoclasts and bone marrow cells. A special structure on the cell membranes of osteoclasts was observed between an osteoclast and a cytoplasmic process of osteoblast/stroma cells, and this cell membrane was coated with electron dense or bristle-like structures. These bristle-like structures were very similar to those of coated pits. The present results show that the coated pit-like structure plays an important role in cell-cell interaction between osteoclasts and osteoblasts/stroma cells in vitro, and suggest that macromolecules binding to the osteoclast-surface receptor via ligands, accumulate in the coated pits, and enter the osteoclast as receptor-macromolecule complexes in endocytic vesicles.

Distribution of the excretory ducts in the rat palatine gland during postnatal development　　　　　　　　　　　　　　　
Nakamura S, Takahashi S, Shinzato K, Wakita M, Morita M
Hokkaido Journal of Dental Science, 23, 60, 64, 2002年, ［査読有り］
英語, 研究論文（学術雑誌）

Apoptosis and proliferation of myoepithelial cells in atrophic rat submandibular glands
S Takahashi, S Nakamura, K Shinzato, T Domon, T Yamamoto, M Wakita
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 49, 12, 1557, 1563, HISTOCHEMICAL SOC INC, 2001年12月, ［査読有り］
英語, 研究論文（学術雑誌）, This study was designed to determine whether apoptosis and proliferation of myoepithelial cells occur in atrophic rat submandibular glands. The excretory duct of the right submandibular gland was doubly ligated with metal clips. The atrophic right submandibular glands removed after 1-28 days of duct ligation were investigated using immunohistochemical double staining for actin as a marker for myoepithelial cells and proliferating cell nuclear antigen (PCNA) as a marker for proliferating cells, double staining for actin immunohistochemistry, nick end-labeling (TUNEL) as a marker for apoptotic cells, and transmission electron microscopy (TEM). A few PCNA- and no TUNEL-positive myoepithelial cells were found in the control submandibular glands taken from animals with no operation. In the experimental glands, PCNA-positive myoepithelial cells were common 2 and 3 days after duct ligation and then decreased in number. TUNEL-positive myoepithelial cells appeared at 2 days and were observed most frequently at 5 days. Apoptotic myoepithelial cells were also identified by TEM. These observations suggest that both apoptosis and proliferation of myoepithelial cells occur, especially in the early phase of atrophy, in the rat submandibular gland.

Postnatal growth of the rat palatine gland
S Nakamura, S Takahashi, M Wakita, M Morita
TISSUE & CELL, 33, 6, 614, 620, CHURCHILL LIVINGSTONE, 2001年12月, ［査読有り］
英語, 研究論文（学術雑誌）, To elucidate how the palatine glands grow postnatally, the palatine glands of rats from 0 to 8 weeks of age were investigated histologically and immunohistochemically. Under light microscope, three dimensions of the right part of the palatine glands were measured and the total number of excretory ducts of the glands was counted from the parasagittal serial sections. immunohistochernistry with anti-5-bromo-2'-deoxyuridine (BrdU) monoclonal antibody was also employed to detect the cellular proliferative activity. At birth (0 weeks), the palatine glands consisted of ducts and immature acini. The ducts in the glands were connected with excretory ducts. After 2 weeks, there was no duct in the glands. Most acinar cells became mature as mucous cells and took the form of tubulo-acini connected directly with excretory ducts. In the posterior region of the glands, serous acinar cells forming demilunes were occasionally seen. All three dimensions of the palatine glands became longer, and the number of excretory ducts tended to increase. Immunohistochemistry showed acinar and duct cells were highly proliferative in early stage of postnatal life and their proliferative activity decreased thereafter. This study demonstrated that immature rat palatine glands of newborn rats grow three-dimensionally during maturation, and that the parenchymal cell proliferation contributes to the growth of the rat palatine glands. In addition, it is suggested that the glandular tissue arises from the excretory ducts formed postnatally. (C) 2001 Harcourt Publishers Ltd.

The fibrillar structure of the cemento-dentinal junction in different kinds of human teeth
T Yamamoto, T Domon, S Takahashi, MN Islam, R Suzuki
JOURNAL OF PERIODONTAL RESEARCH, 36, 5, 317, 321, MUNKSGAARD INT PUBL LTD, 2001年10月, ［査読有り］
英語, 研究論文（学術雑誌）, The cemento-dentinal junction was examined in human maxillary incisors, canines and premolars by scanning electron microscopy combined with NaOH maceration. The NaOH maceration was used to remove interfibrillar substances and to observe details of the fibrillar architecture. The teeth were half-sectioned longitudinally, demineralized and macerated for 3-4 days or for 10-14 days. In the 3-4 day-macerated specimens, longitudinal sections of the cemento-dentinal junction were examined. In the 10-14 day-macerated specimens, the cementum was detached and the inner cementum surface facing the cemento-dentinal junction was examined. Observations suggested that cemental fibrils intermingle with dentinal fibrils only in places at the cemento-dentinal junction in both acellular and cellular cementum. These structural features were consistent in all kinds of teeth investigated here. Using human molars, we have previously proposed that the adhesion of proteoglycans is a main factor for the cemento-dentinal attachment and that the fibril intermingling between dentin and cementum is an accessory or secondary factor. The present study suggests that this applies to other kinds of human teeth.

A resin embedding method for transparent teeth with ink-infiltrated pulp cavities
T Yamamoto, T Domon, S Takahashi, MN Islam, R Suzuki
ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER, 183, 5, 481, 483, URBAN & FISCHER VERLAG, 2001年09月, ［査読有り］
英語, 研究論文（学術雑誌）, This study was designed to evaluate whether resin embedded transparent teeth are as convenient to use as classical transparent teeth. For this purpose demineralized human teeth were divided into coronal and radical portions, and pulp tissue was extracted from the pulp chamber and root canals, into which drawing ink was injected. After dehydration, the specimens were made transparent in methyl salicylate and immersed in polyester resin. The divided portions were recombined at the polymerization. The resin embedded teeth maintained transparency and the black-stained pulp chamber and root canals showed morphological details. The resin embedded specimens could be handled manually and observed freely from any angle. Previously, transparent teeth have been observed in transparent media through a capped glass bottle. In this respect the resin embedding method is superior to the classical method. The new method will be helpful for investigating root canal morphology.

The nature and function of mononuclear cells on the resorbed surfaces of bone in the reversal phase during remodeling
T Domon, R Suzuki, K Takata, Y Yamazaki, S Takahashi, T Yamamoto, M Wakita
ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER, 183, 2, 103, 110, URBAN & FISCHER VERLAG, 2001年03月, ［査読有り］
英語, 研究論文（学術雑誌）, In a reversal phase of bone remodeling many mononuclear cells appear on the resorbed surfaces of bone with characteristic reversal lines as revealed by transmission electron microscopy (TEM). However, these mononuclear cells have been variously hypothesized or reported. The present study examined the TEM features on the resorbed surfaces of three calcified connective tissues, and aimed to clarify the nature and function of the mononuclear cells in a reversal phase. Dentine slices cultured with isolated osteoclasts, human deciduous teeth, and rat mandibles were used in this study. Specimens were fixed, decalcified, and then embedded in Epon 812, and sectioned into 0.1-mum-thick ultrathin sections. The ultrathin sections were stained with uranyl acetate and lead citrate, and then examined by TEM. Many sharply pointed collagen fibrils with striation were observed exposed on the resorbed surfaces of cultured dentine slices, but there were neither cells nor reversal lines. The same features were observed on the root dentine surfaces of human deciduous teeth. Under many mononuclear cells in a reversal phase of remodeling, reversal lines were seen on the resorbed surfaces of rat mandibles, but there were no striated collagen fibrils exposed on the bone surfaces. The alternation of the TEM features on the resorbed surfaces before and after the participation of mononuclear cells in a reversal phase of remodeling suggests the nature and function of these cells: they participate in both degrading the demineralized and disrupted matrix left on the resorbed surfaces and forming reversal lines there.

The initial attachment of cemental fibrils to the root dentin surface in acellular and cellular cementogenesis in rat molars
T Yamamoto, T Domon, S Takahashi, MN Islam, R Suzuki
ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER, 183, 2, 123, 128, URBAN & FISCHER VERLAG, 2001年03月, ［査読有り］
英語, 研究論文（学術雑誌）, To elucidate the initial attachment mechanism of cemental fibrils to the root dentin surface in acellular and cellular cementogenesis, developing rat molars were observed by light microscopy and scanning electron microscopy combined with NaOH maceration. The NaOH maceration was used to observe details of the positional association of cemental and dentinal fibrils during cementogenesis. An initial hematoxylin stained, cementum layer began to form on the root dentin surface with the first dentin mineralization in both acellular and cellular cementogenesis. The initial attachment of cemental fibrils to the dentin surface also began at this point. At the initial attachment the intermingling of cemental and dentinal fibrils occurred only in places. With advanced cementogenesis the initial cementum layer became the fibril-poor cemento-dentinal junction. This suggests that cemental fibrils attach on the initial cementum layer, and not directly on dentinal fibrils, so that the layer results in the fibril-poor cemento-dentinal junction. The present study suggests that an intervening adhesive is necessary for the cemento-dentinal attachment at any stage of cementogenesis in rat molars.

Electron microscopic study of mineralized nodules formed in vitro by isolated featal rat calvaria cells in the absence of ascorbic acid and Na-beta-glycerophosphate　　　　　　　　　　　　　　　
Domon T, Hisada Y, Yoshimura Y, Matsumoto A, Takahashi S, Yamamoto T, Wakita M
Dentistry in Japan, 37, 10, 15, 2001年, ［査読有り］
英語, 研究論文（学術雑誌）

Apoptosis and mitosis of parenchymal cells in the duct-ligated rat submandibular gland
S Takahashi, S Nakamura, R Suzuki, N Islam, T Domon, T Yamamoto, M Wakita
TISSUE & CELL, 32, 6, 457, 463, CHURCHILL LIVINGSTONE, 2000年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Apoptosis and proliferation of parenchymal cells during atrophy of rat submandibular gland induced by double duct ligation were investigated using immunohistochemistry for proliferating cell nuclear antigen (PCNA), terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labelling (TUNEL) and transmission electron microscopy (TEM). At 2 and 3 days after ligation, increased PCNA positive cells and mitoses were seen in ducts; thereafter PCNA positive cells decreased in number. At 3 and 4 days, the acinar cell population rapidly decreased, with many remaining TUNEL positive acinar cells. During this period, TEM showed typical apoptotic acinar cells that were phagocytosed by adjacent acinar cells or intraepithelial macrophages, After 7 days, most acinar cells had disappeared, leaving prominent residual ducts; a few acinar cells remained, especially at the lobule periphery. Submandibular gland duct ligation thus induced marked depletion of acinar cell by apoptosis and a concurrent short-lived cycle of duct cell proliferation. (C) 2000 Harcourt Publishers Ltd.

The fibrillar structure of cementum and dentin at the cemento-dentinal junction in rat molars
T Yamamoto, T Domon, S Takahashi, MN Islam, R Suzuki
ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER, 182, 6, 499, 503, URBAN & FISCHER VERLAG, 2000年11月, ［査読有り］
英語, 研究論文（学術雑誌）, The cemento-dentinal junction was examined in demineralized rat molars with complete roots by scanning electron microscopy combined with NaOH maceration. It is established that the NaOH maceration removes interfibrillar substances and cells from connective tissues selectively without structural damage to collagen fibrils, The cementum was detached from the dentin by the maceration. The inner cementum surface facing the dentin and the outer dentin surface facing the cementum were observed, In acellular cementum, both the outer dentin surface and the inner cementum surface had a smooth appearance, There was little indication of fibrils intermingling between dentin and cementum. Tn contrast, both the inner cementum surface and outer dentin surface in cellular cementum had an uneven appearance due to the irregular arrangement of collagen fibrils. Point-like protrusions of fibril bundles were observed on both surfaces. Some (not all) of these point-like protrusions appeared to correspond to places of fibrillar intermingling between dentin and cementum.

The fibrillar structure of cement lines on resorbed root surfaces of human teeth
T Yamamoto, T Domon, S Takahashi, R Suzuki, MN Islam
JOURNAL OF PERIODONTAL RESEARCH, 35, 4, 208, 213, MUNKSGAARD INT PUBL LTD, 2000年08月, ［査読有り］
英語, 研究論文（学術雑誌）, The cement lines between reparative cementum and resorbed dentin or cementum in human teeth were observed by light microscopy and scanning electron microscopy combined with NaOH maceration. The NaOH maceration was used to remove interfibrillar substances and to observe the fibrillar architecture of the cement lines directly. Light microscopy showed that the cement lines were rich in proteoglycans with mucopolysaccharides, but deficient in collagen fibrils. The cement lines were artificially broken after treatment with hyaluronidase, which digests some of the mucopolysaccharides, but digests no collagen fibrils. Scanning electron microscopy showed that fibril intermingling occurred only in some places between reparative cementum and resorbed tissue. These findings suggested that the proteoglycans in cement Lines mediate the attachment between new and old mineralized tissue.

Twisted plywood structure of an alternating lamellar pattern in cellular cementum of human teeth
T Yamamoto, T Domon, S Takahashi, N Islam, R Suzuki
ANATOMY AND EMBRYOLOGY, 202, 1, 25, 30, SPRINGER VERLAG, 2000年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Human cellular cementum was examined by scanning electron microscopy to elucidate the manner of the alternate lamellar pattern forming the cellular cementum. Specimens were demineralized, trimmed with a freezing microtome, and treated by NaOH-maceration. This procedure was chosen to avoid artifacts in the fibril arrangement, and to study the fibrous architecture in detail. For comparison, non-demineralized, polished and HCl-etched specimens were also prepared. In the NaOH-macerated specimens, the lamellar pattern of the cellular cementum conformed to the twisted plywood principle of bone lamellation with a periodic rotation of matrix fibrils resulting in an alternating lamellar pattern. In contrast, matrix fibrils were irregularly arranged without indication of rotation of matrix fibrils in the polished and etched specimens. Our results suggest that polishing and etching procedures cause damage to fibrils and fibril arrangement.

The fibrous structure of the cemento-dentinal junction in human molars shown by scanning electron microscopy combined with NaOH-maceration
T Yamamoto, T Domon, S Takahashi, MN Islam, R Suzuki
JOURNAL OF PERIODONTAL RESEARCH, 35, 2, 59, 64, MUNKSGAARD INT PUBL LTD, 2000年04月, ［査読有り］
英語, 研究論文（学術雑誌）, The cemento-dentinal junction was studied in acellular and cellular cementum of human mandibular third molars by scanning electron microscopy combined with NaOH-maceration. Scanning electron microscopy with NaOH-maceration was applied to observe the fibrous structure in detail through long sections of the cemento-dentinal junction. In macerated specimens, the cemento-dentinal junction was a fibril-poor groove. Some cemental fibrils or fibril bundles penetrated the groove and appeared to intermingle with dentinal fibrils. Prolonged maceration caused detachment of the cemento-dentinal junction irrespective of fibril intermingling allowing observation of the inner cementum surface facing the root dentin. Observations suggested that the fibril intermingling was point-like and present only in places at the cemento-dentinal junction. It was established that NaOH-maceration removes interfibrillar substances effectively in connective tissues and does no damage to the collagen fibril structure and architecture. This study showed the 3-dimensional fibrous structure of the cemento-dentinal junction in human mandibular third molars, and suggested that interfibrillar adhesive substances are more important than the fibril intermingling for the cemento-dentinal attachment.

The structure of the cemento-dentinal junction in rat molars
T Yamamoto, T Domon, S Takahashi, NMD Islam, R Suzuki, M Wakita
ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER, 182, 2, 185, 190, URBAN & FISCHER VERLAG, 2000年03月, ［査読有り］
英語, 研究論文（学術雑誌）, The cemento-dentinal junction was observed in the acellular and cellular cementum of rat molars by light and scanning electron microscopy. Scanning electron microscopy, combined with NaOH maceration, was used to observe the fibrous architecture directly in this region. Light microscopy revealed that the cemento-dentinal junction contains fewer collagen fibrils and more proteoglycans than the cementum and dentin. Scanning electron microscopy also showed that fibril intermingling is found only in some regions of the fibril-poor junction in macerated specimens. Prolonged maceration breaks down the cemento-dentinal junction in spite of the fibril intermingling. Only macerated specimens showed detachment here. It was established that NaOH maceration removes interfibrillar substances effectively, and does not damage the fibril structure or architecture. This suggests that the adhesion of proteoglycans is more important than fibril intermingling for preserving the cemento-dentinal attachment in the rat molar.

Ultrastructural study of the root dentine surface resuming resorption on human deciduous teeth
T Domon, M Osanai, Y Yawaka, R Suzuki, S Takahashi, T Yamamoto, M Wakita
ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER, 182, 2, 175, 184, URBAN & FISCHER VERLAG, 2000年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Resorption of deciduous teeth is not continuous, but alternates with periods of repair or rest. Dentine surfaces in periods of rest or repair resume resorption by odontoclasts during physiological root resorption of the deciduous teeth. However, no observations of such dentine surfaces have been shown. The characteristic feature of the dentine surfaces resuming resorption remains unknown. Tartrate-resistant acid phosphatase activity (TRAP) was detected on human deciduous teeth. The root resorbing surfaces on these teeth were photographed with a whole-mount light microscope, and the photographed areas were serially sectioned into 0.5 mu m semithin sections. Preodontoclasts and odontoclasts were three-dimensionally reconstructed. On root resorbing surfaces, areas with small scattered TRAP-positive cells were observed among areas with many TRAP-positive resorbing odontoclasts and TRAP-negative areas. The sections showed that areas with small scattered TRAP-positive cells have features similar to those of TRAP-negative areas, but there were three kinds of characteristic TRAP-positive cells: preodontoclasts, odontoclasts forming small lacunae, and preodontoclasts and odontoclasts with cytoplasmic processes extending to the dentine surface, which is covered with cells. These results suggest that the areas with small scattered TRAP-positive cells could be at the stage of resuming resorption, and show that the presence of preodontoclasts and odontoclasts with cytoplasmic processes extending to the covered dentine surface is a characteristic feature of the dentine surface at this stage.

The fibrillar architecture of coronal and root dentine surfaces in human teeth　　　　　　　　　　　　　　　
Yamamoto T, Domon T, Takahashi S, Islam N.M, Suzuki R, Wakita M
Hokkaido Journal of Dental Science, 21, 359, 364, 2000年, ［査読有り］
英語, 研究論文（学術雑誌）

The resorption of inorganic and organic surfaces of human tooth enamel by cultured osteoclasts　　　　　　　　　　　　　　　
Domon T, Suzuki R, Yamazaki Y, Fukui A, Takahashi S, Yamamoto T, Wakita M
Hokkaido Journal of Dental Science, 21, 374, 380, 2000年, ［査読有り］
英語, 研究論文（学術雑誌）

Changing myoepithelial cell distribution during regeneration of rat parotid glands.
S Takahashi, S Nakamura, R Suzuki, T Domon, T Yamamoto, M Wakita
INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, 80, 5, 283, 290, BLACKWELL SCIENCE LTD, 1999年10月, ［査読有り］
英語, 研究論文（学術雑誌）, The distribution of the myoepithelial cells during regeneration of the rat parotid gland after atrophy induced by one week of parotid duct ligation was investigated by immunohistochemistry for actin and transmission electron microscopy (TEM). Immunohistochemically, residual ducts were surrounded by actin-positive cells when clips were removed from the duct. Three days later, most of the newly termed acini originating from the residual ducts were also embraced by actin-positive cells. After 10 days, actin-positivity tended to be seen as dots around acini that decreased in number day by day. On day 21 actin-positive cells mainly surrounded intercalated ducts with only a few positive reactions identified at the acinar periphery. Electron microscopically, residual ducts and newly formed acini were peripherally embraced by myoepithelial cells before day 5. After day 7, shift of myoepithelial cells from the periphery of acini to the duct-acinar junctional region was identified. Then few myoepithelial cells were identified at the periphery of acini. These observations indicate that myoepithelial cells migrate from the acinar periphery to the duct-acinar junctional region during rat parotid regeneration, and that such behaviour is closely related to that seen during rat parotid development.

The structure and function of the cemento-dentinal junction in human teeth
T Yamamoto, T Domon, S Takahashi, N Islam, R Suzuki, M Wakita
JOURNAL OF PERIODONTAL RESEARCH, 34, 5, 261, 268, MUNKSGAARD INT PUBL LTD, 1999年07月, ［査読有り］
英語, 研究論文（学術雑誌）, The structure and function of the cemento-dentinal junction were studied in human molars by light and electron microscopy. The cemento-dentinal junction was an approximately 1-3-mu m-thick layer full of proteoglycans with mucopolysaccharides but containing fewer collagen fibrils than the root dentin and cementum. In places, cemental fibrils crossed the cemento-dentinal junction. These fibrils appeared to intermingle with dentinal fibrils. By enzymatic treatment of decalcified specimen with hyaluronidase and trypsin, the cemento-dentinal junction decreased or lost staining affinity to toluidine blue. Prolonged treatment caused the separation of cementum from the root dentin during routine histological processes. These data suggest that the adhesion of proteoglycans is more important than the intermingling of dentinal and cemental fibrils for the cemento-dentinal attachment.

The structure and function of periodontal ligament cells in acellular cementum in rat molars
T Yamamoto, T Domon, S Takahashi, N Islam, R Suzuki, M Wakita
ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER, 180, 6, 519, 522, GUSTAV FISCHER VERLAG, 1998年12月, ［査読有り］
英語, 研究論文（学術雑誌）, To elucidate the structure and function of periodontal ligament cel:ls at the periodontal ligament-cementum interface in advanced acellular cementogenesis, the cervical regions of molars in rats aged 6 weeks were observed by light and electron microscopy. The light and transmission electron microscopy showed the periodontal ligament cells to be elongated between dense, well-developed principal fibers. The transmission and scanning electron microscopy showed that these cells extended wing-like projections from the lateral surface, forming cylindrical compartments surrounding the principal fibers. In addition, finger-like projections extended toward the cementum from the cementum-facing ends. The main results suggest the following: at the periodontal ligament-cementum interface, the periodontal ligament cells maintain the architecture of the principal fibers by means of extracellular compartments. The arrangement of fingerlike projections results in the formation of acellular cementum containing only Sharpey's fibers as a fibrous component.

Increase in odontoclast nuclei number by cell fusion: A three-dimensional reconstruction of cell fusion of human odontoclasts
T Domon, M Yasuda, M Osanai, R Suzuki, S Takahashi, T Yamamoto, M Wakita
ANATOMICAL RECORD, 252, 3, 462, 471, WILEY-LISS, 1998年11月, ［査読有り］
英語, 研究論文（学術雑誌）, Osteoclasts and odontoclasts are known to increase their nuclear number by fusion of mononuclear precursors. However, the pattern of fusion remains morphologically unclear. One lower right deciduous canine of an 8-year-old male was investigated. Tartrate-resistant acid phosphatase activity (TRAP) positive cells on the resorbing surface of the tooth were serially sectioned into 0.5 mu m-thick semithin sections. The sections were photographed, and cells possessing a light microscopic brush border facing a resorptive lacuna were identified as odontoclasts. Fourteen odontoclasts appearing as a continuous figure of cellular membrane between cells on one section were three-dimensionally reconstructed using NIKON COSMOZONE 2SA. A criterion for fusion was established in this study requiring that there must be two or more nucleated cells which contacted each other at one site only in the three-dimensional reconstruction. Among 14 reconstructed cells, 10 odontoclasts satisfied the criterion for fusion. The observations of the three-dimensional structures of these odontoclasts showed that mononuclear and multinucleated odontoclasts participated in fusion. Cell fusion occurred between resorbing odontoclasts and cells not forming lacunae, and between resorbing odontoclasts. A case of odontoclastic fusion among three cells was also observed. The results establish that fusion resulting in multinucleation occurred among various odontoclasts with different numbers of nuclei including mononuclear odontoclasts. Anat. Rec. 252:462-471, 1998. (C) 1998 Wiley-Liss, Inc.

Origin of acinar cell regeneration after atrophy of the rat parotid induced by duct obstruction
S Takahashi, E Schoch, NI Walker
INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, 79, 5, 293, 301, BLACKWELL SCIENCE LTD, 1998年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Acinar cell regeneration in the rat parotid gland after atrophy induced by a one week period of duct obstruction was examined using histology, immunohistochemistry and transmission electron microscopy (TEM). For immunohistochemistry, antibodies to 5-bromo-2'-deoxyuridine (BrdU), injected one hour before tissue collection, and cytokeratin were employed. When clips were removed from the duct, only ductal epithelial cells remained; all acinar cells had been deleted. Some duct cells were BrdU positive. After three days, newly-formed acini comprising immature acinar cells had appeared; many of the cells were BrdU positive and mitotic figures were readily identified. Thereafter progressive acinar cell maturation and proliferation occurred, parotid gland weight returning to control levels by 7 days. Peak BrdU labelling indices for duct and acinar cells were on days 0 and 4, respectively. By TEM, cytoplasmic organelles in epithelial cells of transitional duct-acinar structures seen at 2 days were poorly developed. Immature acinar cells seen on day 3 contained zymogen granules and had increased endoplasmic reticulum and mitochondria. By day 5, maturing acinar cells had abundant endoplasmic reticulum and zymogen granules, resembling acinar cells in control glands. These observations indicated origin of acinar cell precursors from duct cells during regeneration of the acinar cell-free atrophic gland. Subsequent expansion of the acinar cell population was dependent on maturation and proliferation of these newly-formed cells.

The regulation of fiber arrangement in advanced cellular cementogenesis of human teeth
T Yamamoto, T Domon, S Takahashi, NMD Islam, R Suzuki, M Wakita
JOURNAL OF PERIODONTAL RESEARCH, 33, 2, 83, 90, MUNKSGAARD INT PUBL LTD, 1998年02月, ［査読有り］
英語, 研究論文（学術雑誌）, This study observed cellular cementum in fully formed human premolars by light and electron microscopy to elucidate how cementoblasts regulate the fiber arrangement in cementum. Cementoblasts had wing-like processes encircling the principal fibers, where Sharpey's fibers were dense. On the cementum-facing side, wing-like processes were segmented into finger-like processes in parallel with the cementum surface. Observations suggested that with the segmentation intrinsic fibers appeared around principal fibers in close association with finger-like processes. Where Sharpey's fibers were few or absent, where intrinsic fibers were the main fibrous element of the cementum, cementoblasts had only few or no wing-like processes, but had finger-like processes not associated with the wing-like processes on the cementum-facing side. On the basis of the origin of the finger-like processes the main results suggest that there are two kinds of cementoblasts: one has finger-like processes associated with wing-like processes and secretes intrinsic fibers from the finger-like processes to incorporate the principal fibers for tooth support. The second type has finger-like processes not associated with wing-like processes, this type secretes intrinsic fibers from the finger-like processes to adjust the cementum thickness.

Three-dimensionsl reconstruction of the regenerating duct system in rat submandibular glands damaged by YAG laser irradiation
Takahashi S, Domon T, Yamamoto T, Wakita M
Hokkaido Journal of Dental Science, 19, 1, 63, 69, 1998年, ［査読有り］
英語, 研究論文（学術雑誌）

Mononuclear odontoclast participation in tooth resorption: The distribution of nuclei in human odontoclasts
T Domon, M Osanai, M Yasuda, E Seki, S Takahashi, T Yamamoto, M Wakita
ANATOMICAL RECORD, 249, 4, 449, 457, WILEY-LISS, 1997年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Osteoclasts and odontoclasts have been considered multinucleated giant cells which resorb hard tissue by ruffled borders, Recently, the authors reported the presence of a mononuclear osteoclast and odontoclast with a ruffled border. However, the relative frequency of such cells and the distribution of the number of nuclei including mononuclear cells in them have not been elucidated. Six human deciduous teeth were used in this study. After fixation and decalcification, tartrate-resistant acid phosphatase (TRAP) activity was detected with the azo dye method, and then TRAP-positive cells were observed on resorbing areas of teeth by light microscopy. The cells for investigation were serially sectioned by semithin sections to observe the presence of resorptive lacuna and the number of nuclei. The TRAP activity was detected in both multinucleated and mononuclear odontoclasts from serial semithin sections, and 242 TRAP-positive cells which formed lacunae on dentin were investigated to determine the frequency distribution of the number of nuclei, The mean number of nuclei per cell was 5.3, and median was 4, Only 2.9% of odontoclasts were mononucleus and 93.8% had 10 or fewer nuclei. The majority of odontoclasts forming lacunae on the dentin were cells with 10 or fewer nuclei, and mononuclear odontoclasts participated in human deciduous tooth resorption together with multinucleated ones. (C) 1997 Wiley-Liss, Inc.

Formation of an alternate lamellar pattern in the advanced cellular cementogenesis in human teeth
T Yamamoto, T Domon, S Takahashi, M Wakita
ANATOMY AND EMBRYOLOGY, 196, 2, 115, 121, SPRINGER VERLAG, 1997年08月, ［査読有り］
英語, 研究論文（学術雑誌）, The formation of an alternate lamellar pattern in the advanced stage of cellular cementogenesis in human molars was examined by light and electron microscopy. In longitudinal ultrathin sections, longitudinally oriented intrinsic fibril bundles appeared in close and parallel association with slender processes of cementoblasts on the cementum. Where transversely oriented intrinsic fibril bundles appeared, cementoblasts formed indentations to enclose the fibril bundles. Cytoplasmic fragments were also enclosed in the indentations. Scanning electron microscopy indicated that cementoblasts have developed two types of processes on their cementum-facing side - ridge-and finger-like. The cementoblasts formed groove-like compartments by ridge-like processes in cooperation with other cementoblasts. The compartments formed groups, and in each group the compartments were arranged in the same direction. The finger-like processes were arranged in parallel with the ridge-like processes in the compartments. These observations suggest that: (1) slender processes and cytoplasmic fragments are longitudinally and transversely cut fingerlike processes, respectively; (2) the cellular indentations are transversely cut groove-like compartments; (3) the cementoblasts regulate the intrinsic fiber arrangement by the two types of processes; (4) the cementoblasts move the two types of processes synchronously and periodically to cause an alternate change in the intrinsic fiber arrangement. This dynamic sequence results in the alternate lamellar pattern of cellular cementum.

Regeneration of myoepithelial cells in rat submandibular glands after yttrium aluminium garnett laser irradiation
S Takahashi, T Domon, T Yamamoto, M Wakita
INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, 78, 2, 91, 99, BLACKWELL SCIENCE LTD, 1997年04月, ［査読有り］
英語, 研究論文（学術雑誌）, The regeneration of myoepithelial cells in rat submandibular salivary gland after partial irradiation with yttrium aluminium garnett (YAG) laser was investigated. The irradiated glands were examined immunohistochemically for actin, histochemically for alkaline phosphatase (ALP), and by transmission electron microscopy (TEM). In control glands, myoepithelial cells were positive for actin and ALP. Electron microscopically, the positive reaction for actin was associated with the myofilaments of myoepithelial cells, and the plasma membrane of myoepithelial cells was positive for ALP. One day after YAG laser irradiation, the irradiated region was necrotic. By 5 days, duct-like structures and epithelial clusters were observed at the interface between the necrotic zone and the remaining undamaged glands; immature acini appeared after 7 days. No reaction in duct-like structures or epithelial clusters to actin or ALP was recognizable by 5 days. However, at 7 days, actin and ALP-positive spindle cells appeared at the periphery of the duct-like structures and immature acini. After 10 days, both actin-positive and ALP-positive cells increased in number. These observations indicate that during regeneration, actin-positive and ALP-positive cells regenerate myoepithelial cells, and it is suggested that this differentiation to myoepithelial cells is closely related to that of luminal to acinar cells. In addition, TEM observations indicate that regenerated myoepithelial cells originated from the basal cells of duct-like structures.

Cellular cementogenesis in rat molars: The role of cementoblasts in the deposition of intrinsic matrix fibers of cementum proper
T Yamamoto, T Domon, S Takahashi, M Wakita
ANATOMY AND EMBRYOLOGY, 193, 5, 495, 500, SPRINGER VERLAG, 1996年05月, ［査読有り］
英語, 研究論文（学術雑誌）, The formation of intrinsic fibers was examined in the advanced stage of rat cellular cementogenesis by light and electron microscopy. Using scanning electron microscopy, cementoblasts showed wing-like processes, partly encircling principal fibers. At the cementum-facing side of the cells these processes showed segmentation into finger-like processes, arranged in parallel with the cementum surface. Transmission electron microscopy showed many cytoplasmic fragments around intrinsic fibers at the cementum surface. These fragments contained microtubules and collagenous secretory granules that were arranged in parallel with the cementum surface and the intrinsic fibers. The wing-like processes contained microtubules and secretory granules that were arranged perpendicularly to the cementum surface and in parallel with the principal fibers. These observations suggest that: (1) the cytoplasmic fragments are cross-sectioned finger-like processes; (2) cementoblasts secrete intrinsic fibers from the finger-like processes and additional principal fibers from the wing-like processes; (3) cementoblasts constantly shorten their wing-like processes by forming finger-like processes. This development starts at the side facing the cementum and proceeds towards the periodontal ligament. With the segmentation, the cementoblasts change the arrangement of secretory granules to secrete intrinsic fibers around preformed principal fibers.

COMPARATIVE-STUDY OF THE INITIAL GENESIS OF ACELLULAR AND CELLULAR CEMENTUM IN RAT MOLARS
T YAMAMOTO, T DOMON, S TAKAHASHI, M WAKITA
ANATOMY AND EMBRYOLOGY, 190, 6, 521, 527, SPRINGER VERLAG, 1994年12月, ［査読有り］
英語, 研究論文（学術雑誌）, The initial genesis of acellular and cellular cementum was examined in rat molars by light and electron microscopy. Before root dentinogenesis, flattened dental follicle cells formed compartments by regularly arranged cellular processes which demarcated collagen fibril bundles oriented in parallel with the root long axis in both of the two kinds of cementum. After this stage, compartments disappeared from the dental follicle cells, which became elongated and polarized, with the cytoplasmic side facing toward the root surface in the acellular cementogenesis. Fibril bundles, oriented in parallel with the root long axis, decreased in number, and principal fibers appeared. Some principal fibers were attached on the first acellular cementum. Observations susggested that the fibril bundles, which had been oriented in parallel with the root long axis, were reoriented to merge into the principal fibers. In cellular cementogenesis, the dental follicle cells continued to hold the fibril bundles in cellular compartments. The regular processes were transformed into randomly oriented, finger-like processes. At the same time, fibers, which may be secreted from the finger-like processes, appeared around the preformed fibril bundles oriented in parallel with the root long axis. The different cellular behavior may result in the different fiber arrangement of acellular and cellular cementum.

ELECTRON-MICROSCOPIC AND HISTOCHEMICAL-STUDIES OF THE MONONUCLEAR ODONTOCLAST OF THE HUMAN
T DOMON, K SUGAYA, Y YAWAKA, M OSANAI, Y HANAIZUMI, S TAKAHASHI, M WAKITA
ANATOMICAL RECORD, 240, 1, 42, 51, WILEY-LISS, 1994年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Osteoclasts and odontoclasts are multinucleated giant cells which resorb hard tissue by the ruffled borders. Recently, the authors reported the presence of a mononuclear osteoclast with a ruffled border in vitro. However, its presence in vivo has not been shown. To demonstrate the presence of a mononuclear odontoclast in humans, the present study used human deciduous teeth.
Methods: After fixation and decalcification, tartrate-resistant acid phosphatase (TRACPase) activity was detected with the azo dye method, and then TRACPase-positive cells were observed on resorbing areas of teeth. TRACPase-positive cells could be distinguished from other cells by light microscopy, and the cells for investigation were serially sectioned by alternating semithin and ultrathin sections to observe their ultrastructure and three-dimensional organization.
Results: TRACPase activity was detected in both multinucleated odontoclasts and a mononuclear cell from serial sections. By electron microscopy, most of the multinucleated odontoclasts had ruffled borders and clear zones. A mononuclear TRACPase-positive cell with a ruffled border and clear zone was reconstructed three-dimensionally by NIKON COSMOZONE 2SA. The reconstruction showed that this cell had one irregularly shaped nucleus and a wide ring-shaped clear zone and a small ruffled border. Under the ruffled border, this cell formed a small lacuna on the dentin surface. The results suggested that this cell was a mononuclear odontoclast.
Conclusions: The present study concludes that cells with ruffled borders and clear zones observed by transmission electron microscopy can be identified as odontoclasts or osteoclasts irrespective of the number of nuclei.(C) 1994 Wiley-Liss, Inc.

CYTOKERATIN EXPRESSION DURING REGENERATION OF THE INTRALOBULAR DUCT IN RAT SUBMANDIBULAR GLANDS AFTER YAG LASER IRRADIATION
S TAKAHASHI, M WAKITA
ARCHIVES OF HISTOLOGY AND CYTOLOGY, 57, 2, 167, 173, INT SOC HISTOLOGY & CYTOLOGY, 1994年05月, ［査読有り］
英語, 研究論文（学術雑誌）, Changes in the expression of cytokeratin subunits during regeneration of the intralobular duct in partially injured rat submandibular glands were investigated. Limited parts of rat submandibular glands were injured by irradiation with YAG laser. Irradiated glands were investigated histologically and immunohistochemically using anti-cytokeratin monoclonal antibodies, RCK105 and CK19. Irradiated areas became necrotic one day after YAG laser irradiation. At three and five days, duct-like structures and epithelial clusters began to regenerate at the periphery of the remaining lobule. Epithelial clusters without ductal spaces were situated at the terminal portion of the duct-like structures. At seven and ten days, duct-like structures were composed of cuboidal or low columnar cells, and the number of epithelial clusters decreased. Immunohistochemically, cells of intralobular ducts in normal rat submandibular glands reacted to RCK105 and CK19. At three and five days, the epithelial cells of duct-like structures were positive for both antibodies. Many cells in the epithelial clusters showed negative reaction. However, in some epithelial clusters, inner cells and cells facing narrow luminal spaces were positive for both antibodies. At seven and ten days, positive reaction for both antibodies was identified in duct-like structures.
This study showed that cells of the epithelial cluster were less mature than those of the duct-like structure, and that in the epithelial cluster, the inner cells were the first to differentiate into intralobular ductal cells.

REGENERATION OF THE INTRALOBULAR DUCT AND ACINUS IN RAT SUBMANDIBULAR GLANDS AFTER YAG LASER IRRADIATION
S TAKAHASHI, M WAKITA
ARCHIVES OF HISTOLOGY AND CYTOLOGY, 56, 2, 199, 206, INT SOC HISTOLOGY & CYTOLOGY, 1993年06月, ［査読有り］, ［筆頭著者］
英語, 研究論文（学術雑誌）, The present study was performed to understand the regeneration of the intralobular duct and acinus of partially injured salivary glands. Sections of rat submandibular glands irradiated with YAG laser were investigated histologically, and the proliferative activity of regenerating tissue was also investigated immunohistochemically with anti 5-bromo-2'-deoxyuridine (BrdU) monoclonal antibody.
After YAG laser irradiation, duct-like structures continuous to the remaining ducts were regenerated at the periphery of the injured lobule. At the distal end of the duct-like structures, squamous cells were shown to form epithelial clusters. Additionally, immature acinar cells appeared budding off from the duct-like structures. During regeneration, BrdU-positive cells were observed in these duct-like structures, epithelial clusters, and immature acini.
This study showed that duct-like structures, epithelial clusters and immature acini appear during the regeneration process of partially injured lobules, and that each structure proliferated in order to contribute to the rapid regeneration of the salivary gland.

YAGレーザー照射によるラット顎下腺の損傷と修復に関する形態学的研究
髙橋 茂
歯科基礎医学会雑誌, 35, 2, 115, 146, 1993年04月, ［査読有り］, ［筆頭著者, 最終著者, 責任著者］
日本語, 研究論文（学術雑誌）

唾液腺腫瘍の臨床的研究　　　　　　　　　　　　　　　
小野貢伸, 有末 真, 藤原敏勝, 井上農夫男, 河村正昭, 野谷健一, 戸塚靖則, 福田 博, 髙橋 茂, 飯塚 正, 進藤正信, 向後隆男, 雨宮 璋
北海道頭頸部腫瘍, 12, 23, 27, 1991年, ［査読有り］
日本語, 研究論文（学術雑誌）

咀嚼による耳下腺の自己回復における自律神経シグナルの解明と回復に関わる遺伝子の同定　　　　　　　　　　　　　　　
根津顕弘, 髙橋 茂, 加藤志織, 谷村明彦
第68回日本唾液腺学会, 2024年12月07日, 日本語, 口頭発表（一般）

唾液腺の退行性変化におけるアポトーシス ～組織学的視点から～　　　　　　　　　　　　　　　
髙橋 茂
令和6年度北海道歯学会秋季学術大会, 2024年11月20日, 日本語, 口頭発表（招待・特別）
2024年11月20日 - 2024年11月21日, ［招待講演］

咀嚼刺激による耳下腺の自己回復シグナルの解明と回復に関わる遺伝子の同定　　　　　　　　　　　　　　　
根津顕弘, 髙橋 茂, 加藤志織, 谷村明彦
第66回歯科基礎医学会, 2024年11月04日, 日本語, ポスター発表
2024年11月02日 - 2024年11月04日

歯肉由来間葉系幹細胞の細胞特性に対するメカニカルストレスの影響　　　　　　　　　　　　　　　
髙橋智美, 髙橋 茂
第66回歯科基礎医学会, 2024年11月02日, 日本語, ポスター発表
2024年11月02日 - 2024年11月04日

ソフトフード摂取が唾液腺に及ぼす影響　　　　　　　　　　　　　　　
髙橋 茂
第６５回歯科基礎医学会, 2023年09月17日, 日本語, シンポジウム・ワークショップパネル（公募）

液状飼料が成長期ラットの唾液腺神経組織に及ぼす影響　　　　　　　　　　　　　　　
髙橋 茂, 中道祥之, 山本恒之
第６６回日本唾液腺学会, 2022年11月26日, 日本語, 口頭発表（一般）

Effects of liquid diet feeding on growth of nerve in rat salivary glands during growth period　　　　　　　　　　　　　　　
Takahashi S, Nakamichi Y, Yamamoto T
20th International Federation of Associations of Anatomists, 2022年08月05日, 英語

Effects of a liquid diet on growth of nerve in parotid glands of growing rats　　　　　　　　　　　　　　　
Takahashi S., Yamamoto T.
第６３回歯科基礎医学会, 2021年10月11日, 英語, 口頭発表（一般）
2021年10月09日 - 2021年10月11日

Recovery of rat parotid glands atrophied by liquid diet following change of diet　　　　　　　　　　　　　　　
Takahashi S, Takebuchi R, Taniwaki H, Domon T
第６０回歯科基礎医学会, 2018年09月07日, 英語, ポスター発表
［国内会議］

Recovery from atrophy of rat parotid glands by change from liquid diet feeding to pellet diet feeding　　　　　　　　　　　　　　　
Takahashi S, Takebuchi R, Taniwaki H, Domon T
第５９回歯科基礎医学会, 2017年09月18日, 英語, ポスター発表
［国内会議］

液状飼料飼育がラット唾液腺の発育に与える影響に関する形態学的研究　　　　　　　　　　　　　　　
髙橋 茂, 上北広樹, 谷脇裕人, 土門卓文
第６１回日本唾液腺学会, 2016年12月03日, 日本語, 口頭発表（一般）
［国内会議］

Effects of liquid diet on acinar cells in submandibular and sublingual glands of growing rats　　　　　　　　　　　　　　　
Takahashi S, Uekita H, Taniwaki H, Inoue K, Domon T
第５８回歯科基礎医学会, 2016年08月26日, 英語, ポスター発表
［国内会議］

演習科目における遠隔授業の試み　　　　　　　　　　　　　　　
髙橋 茂
北海道地区国立大学教養教育連携実施機構FDフォーラム「発展する遠隔授業」, 2016年02月12日, 日本語, 口頭発表（一般）
［国内会議］

ソフトフード飼育ラット顎下腺・舌下腺の発育に関する組織学的検討　　　　　　　　　　　　　　　
髙橋 茂, 上北広樹, 土門卓文
第６０回日本唾液腺学会, 2015年12月05日, 日本語, 口頭発表（一般）
［国内会議］

Effects of liquid diet on the growth of rat submandibular and sublingual glands　　　　　　　　　　　　　　　
Takahashi S, Uekita H, Inoue K, Domon T
第５７回歯科基礎医学会, 2015年09月13日, 英語, 口頭発表（一般）
［国内会議］

ソフトフード長期摂取がラット耳下腺の発育に及ぼす影響　　　　　　　　　　　　　　　
髙橋 茂, 上北広樹, 加藤剛士, 井上貴一朗, 土門卓文
第５９回日本唾液腺学会, 2014年12月06日, 日本語, 口頭発表（一般）
［国内会議］

液状飼料飼育がラット耳下腺の成長に与える影響について
髙橋 茂, 上北広樹, 加藤剛士, 牛島夏未, 井上貴一朗, 土門卓文
第５６回歯科基礎医学会総会, 2014年09月27日, 日本語, ポスター発表
［国内会議］

液状飼料飼育に対するラット顎下腺および舌下腺の反応について　　　　　　　　　　　　　　　
髙橋 茂, 上北広樹, 加藤剛士, 弓削文彦, 牛島夏未, 井上貴一朗, 土門卓文
第１１８回日本解剖学会総会, 2013年03月30日, 日本語, ポスター発表
［国内会議］

Reaction of submandibular and sublingual glands to liquid diet feeding　　　　　　　　　　　　　　　
Takahashi S, Uekita H, Kato T, Yuge F, Ushijima N, Inoue K, Domon T
6th IADR Pan European Regional Meeting, 2012年09月15日, 英語, 口頭発表（一般）
［国際会議］

Cell proliferation and cell death in atrophic rat parotid glands induced by liquid diet feeding　　　　　　　　　　　　　　　
Takahashi S, Uekita H, Kato T, Yuge F, Ushijima N, Inoue K, Domon T
10th Asia-Pacific Microscopy Conference, 2012年02月06日, 英語, 口頭発表（一般）
［国際会議］

クリッカーの活用で授業を活性化しよう！　　　　　　　　　　　　　　　
髙橋 茂
第４０回北海道大学大学院歯学研究科FD講演会, 2011年12月14日, 日本語, 口頭発表（一般）
［招待講演］, ［国内会議］

液状飼料飼育がラット耳下腺の細胞増殖と細胞死に与える影響について　　　　　　　　　　　　　　　
髙橋 茂, 弓削文彦, 加藤剛士, 牛島夏未, 井上貴一朗, 土門卓文
第５３回歯科基礎医学会総会, 2011年10月02日, 日本語, 口頭発表（一般）
［国内会議］

Atrophic alterations of rat parotid gland induced by liquid diet feeding　　　　　　　　　　　　　　　
Takahashi S, Yuge F, Kato T, Yamada R, Ushijima N, Inoue K, Domon T
第１１６回日本解剖学会総会, 2011年03月29日, 日本語, 口頭発表（一般）
［国内会議］

Effect of liquid diet on cell proliferation in salivary glands　　　　　　　　　　　　　　　
Takahashi S, Wakita M, Yuge F, Katoh T, Ushijima N, Inoue K, Domon T
89th General Session & Exhibition of the IADR, 2011年03月19日, 英語, 口頭発表（一般）
［国際会議］

全学教育科目「唾液のサイエンス」におけるクリッカー使用とその効果について　　　　　　　　　　　　　　　
髙橋 茂, 井上貴一朗, 舩橋 誠, 土門卓文
北海道歯学会平成２２年度春季学術大会, 2010年05月28日, 日本語, 口頭発表（一般）
［国内会議］

唾液腺の障害と修復について　　　　　　　　　　　　　　　
髙橋 茂
北海道歯学会平成２１年度２月例会, 2010年02月18日, 日本語, 口頭発表（招待・特別）
［招待講演］, ［国内会議］

ラット顎下腺萎縮過程におけるBaxとBcl-2の発現とその役割　　　　　　　　　　　　　　　
髙橋 茂, 吉村善隆, 山本恒之
第５０回歯科基礎医学会総会, 2008年09月, 日本語, 口頭発表（一般）
［国内会議］

ラット萎縮顎下腺におけるBcl-2ファミリータンパクの発現について　　　　　　　　　　　　　　　
髙橋 茂, 吉村善隆, 向後隆男, 山本恒之, 脇田 稔
第５２回日本唾液腺学会, 2007年12月, 日本語, 口頭発表（一般）
［国内会議］

唾液腺障害と再生に関する細胞増殖とアポトーシス　　　　　　　　　　　　　　　
髙橋 茂
第４９回歯科基礎医学会総会サテライトシンポジウム, 2007年08月, 日本語, 口頭発表（招待・特別）
［招待講演］, ［国内会議］

Fas/Fasリガンドによる導管障害顎下腺腺房細胞のアポトーシス誘導　　　　　　　　　　　　　　　
髙橋 茂, 向後隆男, 吉村善隆, 中村史朗, 山本恒之, 脇田 稔
第５１回日本唾液腺学会, 2006年12月, 日本語, 口頭発表（一般）
［国内会議］

萎縮顎下腺におけるアポトーシスへのFas/Fasリガンドの関与について　　　　　　　　　　　　　　　
髙橋 茂, 吉村善隆, 向後隆男, 中村史朗, 土門卓文, 山本恒之, 脇田 稔
第４８回歯科基礎医学会総会, 2006年09月, 日本語, 口頭発表（一般）
［国内会議］

萎縮・再生における各種唾液腺の筋上皮細胞増殖活性の相違について　　　　　　　　　　　　　　　
髙橋 茂, 向後隆男, 中村史朗, 土門卓文, 山本恒之, 脇田 稔
第５０回日本唾液腺学会, 2005年12月, 日本語, 口頭発表（一般）
［国内会議］

ラット舌下腺再生過程における筋上皮細胞の分布と形態変化について　　　　　　　　　　　　　　　
髙橋 茂, 向後隆男, 中村史朗, 土門卓文, 山本恒之, 脇田 稔
第４７回歯科基礎医学会総会, 2005年09月, 日本語, 口頭発表（一般）
［国内会議］

Fas and Fas ligand expression inatrohpy of submandibular gland　　　　　　　　　　　　　　　
Takahashi S, Domon T, Yamamoto T, Wakita M
83rd General Session & Exhibition of IADR, 2005年03月, 英語, 口頭発表（一般）
［国際会議］

ラット舌下腺再生における細胞増殖とアポトーシスの関与について　　　　　　　　　　　　　　　
髙橋 茂, 土門卓文, 山本恒之, 脇田 稔
第４９回日本唾液腺学会, 2004年12月, 日本語, 口頭発表（一般）
［国内会議］

硬骨魚類破骨細胞における明帯の微細構造について
土門 卓文, 福井 亜実, 高橋 茂, 山本 恒之, 脇田 稔
Journal of oral biosciences, 2004年09月01日, 歯科基礎医学会, 日本語
2004年09月01日 - 2004年09月01日

萎縮ラット舌下腺回復過程における腺房細胞の再生について　　　　　　　　　　　　　　　
髙橋 茂, 中村史朗, 新里勝宏, 土門卓文, 山本恒之, 脇田 稔
第４６回歯科基礎医学会総会, 2004年09月, 日本語, 口頭発表（一般）
［国内会議］

Mitotic proliferation of myoepithelial cells during regeneration of atrophied rat submandibular glands　　　　　　　　　　　　　　　
Takahashi S, Domon T, Yamamoto T, Wakita M
16th International Congress of the International Federation of Association of Anatomists, 2004年08月, 英語, 口頭発表（一般）
［国際会議］

ラット臼歯無細胞セメント質形成におけるグリコサミノグリカンと骨関連糖蛋白質の局在について
山本 恒之, 土門 卓文, 高橋 茂, 脇田 稔
歯科基礎医学会雑誌, 2003年09月01日, 歯科基礎医学会, 日本語
2003年09月01日 - 2003年09月01日

硬骨魚類サケ破骨細胞の核数の分布について　　　　　　　　　　　　　　　
土門 卓文, 福井 亜実, 大西 康友, 高橋 茂, 山本 恒之, 脇田 稔
歯科基礎医学会雑誌, 2003年09月01日, 歯科基礎医学会, 日本語
2003年09月01日 - 2003年09月01日

Apoptosis and mitosis during regeneration of rat submandibular glands　　　　　　　　　　　　　　　
Takahashi S, Shinzato K, Domon T, Yamamoto T, Wakita M
43rd Annual Meeting of IADR ANZ Division, 2003年09月, 英語, 口頭発表（一般）
［国際会議］

ラット顎下腺再生過程における細胞増殖とアポトーシスについて　　　　　　　　　　　　　　　
髙橋 茂, 新里勝宏, 中村史朗, 土門卓文, 山本恒之, 脇田 稔
第４５回歯科基礎医学会総会, 2003年09月, 日本語, 口頭発表（一般）
［国内会議］

萎縮ラット舌下腺における筋上皮細胞の増殖活性について　　　　　　　　　　　　　　　
髙橋 茂, 新里勝宏, 中村史朗, 土門卓文, 山本恒之, 脇田 稔
第４４回歯科基礎医学会総会, 2002年10月, 日本語, 口頭発表（一般）
［国内会議］

レジン包埋した歯牙透明標本の歯冠復構法
山本 恒之, 土門 卓文, 高橋 茂, イスラム ヌルル, 脇田 稔
歯科基礎医学会雑誌, 2002年09月20日, 歯科基礎医学会, 日本語
2002年09月20日 - 2002年09月20日

萎縮ラット舌下腺における筋上皮細胞の増殖活性について
高橋 茂, 新里 勝宏, 中村 史朗, 土門 卓文, 山本 恒之, 脇田 稔
歯科基礎医学会雑誌, 2002年09月20日, 歯科基礎医学会, 日本語
2002年09月20日 - 2002年09月20日

Apoptosis and mitosis in atrophy of the sublingual gland of rat　　　　　　　　　　　　　　　
Takahashi S, Shinzato K, Domon T, Yamamoto T, Wakita M
11th Biennial Meeting of the International Association of Oral Pathologists, 2002年08月, 英語, 口頭発表（一般）
［国際会議］

Apoptosis and proliferation in atrophic sublingual gland of the rat　　　　　　　　　　　　　　　
Takahashi S, Nakamura S, Shinzato K, Domon T, Yamamoto T, Wakita M
1st International Congress on Salivary Gland Diseases, 2002年01月, 英語, 口頭発表（一般）
［国際会議］

萎縮ラット舌下腺における細胞増殖とアポトーシスについて　　　　　　　　　　　　　　　
髙橋 茂, 新里勝宏, 中村史朗, 土門卓文, 山本恒之, 脇田 稔
第４３回歯科基礎医学会総会, 2001年09月, 日本語, 口頭発表（一般）
［国内会議］

歯牙透明標本のレジン包埋法
山本 恒之, 土門 卓文, 高橋 茂, イスラム ヌルル, 脇田 稔
歯科基礎医学会雑誌, 2001年08月20日, 歯科基礎医学会, 日本語
2001年08月20日 - 2001年08月20日

ラット胎児頭蓋骨由来細胞の長期培養下で形成される石灰化結節の微細構造学的研究
土門 卓文, 吉付 義隆, 松本 章, 高橋 茂, 山本 恒之, 脇田 稔
歯科基礎医学会雑誌, 2001年08月20日, 歯科基礎医学会, 日本語
2001年08月20日 - 2001年08月20日

萎縮ラット舌下腺における細胞増殖とアポトーシスについて
高橋 茂, 新里 勝宏, 中村 史朗, 土門 卓文, 山本 恒之, 脇田 稔
歯科基礎医学会雑誌, 2001年08月20日, 歯科基礎医学会, 日本語
2001年08月20日 - 2001年08月20日

Apoptosis and proliferation of myoepithelial cells inatrophic submandibular gland　　　　　　　　　　　　　　　
Takahashi S, Nakamura S, Shinzato K, Domon T, Yamamoto T, Wakita M
79th General Session & Exhibition of the IADR, 2001年06月, 英語, 口頭発表（一般）
［国際会議］

Cell death and cell proliferation inexperimental obstructive sialadenitis of the rat　　　　　　　　　　　　　　　
Takahashi S
北海道大学大学院歯学研究科・全北大学校歯科大学姉妹校提携１０周年記念学術セミナー, 2000年10月, 英語, 口頭発表（招待・特別）
［招待講演］, ［国際会議］

導管結紮ラット顎下腺における腺房細胞のアポトーシスについて　　　　　　　　　　　　　　　
髙橋 茂, 中村史朗, 鈴木礼子, 土門卓文, 山本恒之, 脇田 稔
第４２回歯科基礎医学会総会, 2000年09月, 日本語, 口頭発表（一般）
［国内会議］

導管結紮ラット顎下腺における腺房細胞のアポトーシスについて
高橋 茂, 中村 史朗, 鈴木 礼子, 土門 卓文, 山本 恒之, 脇田 稔
歯科基礎医学会雑誌, 2000年08月30日, 歯科基礎医学会, 日本語
2000年08月30日 - 2000年08月30日

修復前の骨吸収面上に見られる単核細胞の役割について
土門 卓文, 鈴木 礼子, 山崎 与志紀, イスラム ヌルル, 高橋 茂, 山本 恒之, 脇田 稔
歯科基礎医学会雑誌, 2000年08月30日, 歯科基礎医学会, 日本語
2000年08月30日 - 2000年08月30日

導管結紮ラット顎下腺における細胞増殖と細胞死について　　　　　　　　　　　　　　　
髙橋 茂, 鈴木礼子, イスラム・ヌルル, 土門卓文, 山本恒之, 脇田 稔
第１０５回日本解剖学会総会, 2000年03月, 日本語, 口頭発表（一般）
［国内会議］

導管結さつラット顎下腺における細胞増殖と細胞死について　　　　　　　　　　　　　　　
高橋茂, 鈴木礼子, ヌルル イスラム, 土門卓文, 山本恒之, 脇田稔
解剖学雑誌, 2000年
2000年 - 2000年

破歯細胞と乳歯歯根象牙質表面との三次元接触様式
土門 卓文, 鈴木 礼子, 長内 正数, 高田 賢二, 高橋 茂, 山本 恒之, 脇田 稔
歯科基礎医学会雑誌, 1999年08月20日, 歯科基礎医学会, 日本語
1999年08月20日 - 1999年08月20日

セメント象牙境の構造と機能について
山本 恒之, 土門 卓文, 高橋 茂, イスラム・ヌルル, 鈴木 礼子, 脇田 稔
歯科基礎医学会雑誌, 1999年08月20日, 歯科基礎医学会, 日本語
1999年08月20日 - 1999年08月20日

ラット耳下腺の再生過程における筋上皮細胞の局在について　　　　　　　　　　　　　　　
髙橋 茂, 鈴木礼子, イスラム・ヌルル, 土門卓文, 山本恒之, 脇田 稔
第１０４回日本解剖学会総会, 1999年03月, 日本語, 口頭発表（一般）
［国内会議］

ラット耳下腺の再生過程に関する免疫組織化学的・電子顕微鏡的検討　　　　　　　　　　　　　　　
髙橋 茂, Schoch E, Walker N.I
北海道歯学会平成１０年度春季学術大会, 1998年05月, 日本語, 口頭発表（一般）
［国内会議］

ラット耳下腺再生過程における細胞増殖動態の検討　　　　　　　　　　　　　　　
髙橋 茂, Walker N.I
第１０３回日本解剖学会総会, 1998年03月, 日本語, 口頭発表（一般）
［国内会議］

ラット顎下腺筋上皮細胞の再生に関する免疫組織化学的・酵素組織化学的検討　　　　　　　　　　　　　　　
髙橋 茂, 石 亦文, 長内正数, 土門卓文, 山本恒之, 脇田 稔
北海道歯学会平成８年度春季学術大会, 1996年05月, 日本語, 口頭発表（一般）
［国内会議］

ラット顎下腺筋上皮細胞の再生に関する免疫組織化学的検討　　　　　　　　　　　　　　　
髙橋 茂, 長内正数, 土門卓文, 山本恒之, 脇田 稔
第３７回歯科基礎医学会総会, 1995年09月, 日本語, 口頭発表（一般）
［国内会議］

ラット顎下腺再生過程における再生導管上皮の立体的構造について　　　　　　　　　　　　　　　
髙橋 茂, 長内正数, 土門卓文, 山本恒之, 脇田 稔
第３６回歯科基礎医学会総会, 1994年10月, 日本語, 口頭発表（一般）
［国内会議］

ラット顎下腺小葉内導管の再生について～抗サイトケラチン抗体を用いた免疫組織化学的検討～　　　　　　　　　　　　　　　
髙橋 茂, 脇田 稔
第３９回日本解剖学会東北・北海道連合地方会, 1993年10月, 日本語, 口頭発表（一般）
［国内会議］

ラット顎下腺小葉内導管の再生に関する免疫組織化学的検討　　　　　　　　　　　　　　　
髙橋 茂, 脇田 稔
第３５回歯科基礎医学会総会, 1993年10月, 日本語, 口頭発表（一般）
［国内会議］

ラット顎下腺小葉内の導管・腺房の再生について～5-bromo-2'-deoxyuridine(BrdU)を用いた細胞動態の検討～　　　　　　　　　　　　　　　
髙橋 茂, 脇田 稔
第３８回日本解剖学会東北・北海道連合地方会, 1992年09月, 日本語, 口頭発表（一般）
［国内会議］

ＹＡＧレーザー照射によるラット顎下腺の損傷と修復に関する形態学的研究　　　　　　　　　　　　　　　
髙橋 茂
北海道歯学会平成３年度秋季学術大会, 1991年11月, 日本語, 口頭発表（一般）
［国内会議］

ＹＡＧレーザー照射によるラット顎下腺の損傷と修復についてー第３報：電顕微鏡的研究ー　　　　　　　　　　　　　　　
髙橋 茂, 飯塚 正, 進藤正信, 向後隆男, 雨宮 璋
第４５回日本口腔科学会総会, 1991年05月, 日本語, 口頭発表（一般）
［国内会議］

ＹＡＧレーザー照射によるラット顎下腺の損傷と修復についてー第２報：ＢｒｄＵを用いての検討ー　　　　　　　　　　　　　　　
髙橋 茂, 飯塚 正, 進藤正信, 向後隆男, 雨宮 璋
第３２回歯科基礎医学会総会, 1990年10月, 日本語, 口頭発表（一般）
［国内会議］

5 Cases of adenomatoid odontogenic tumor　　　　　　　　　　　　　　　
Takahashi S, Kobayashi I, Iizuka T, Shindo M, Kohgo T, Amemiya A
5th Biennial Congress of International Association of Oral Pathologist, 1990年, 英語, 口頭発表（一般）
［国際会議］

ＹＡＧレーザー照射によるラット顎下腺の損傷と修復について　　　　　　　　　　　　　　　
髙橋 茂, 飯塚 正, 向後隆男, 雨宮 璋
第３１回歯科基礎医学会総会, 1989年09月, 日本語, 口頭発表（一般）
［国内会議］

頸部郭清術により偶然発見された腺リンパ腫の２例　　　　　　　　　　　　　　　
髙橋 茂, 飯塚 正, 進藤正信, 向後隆男, 雨宮 璋, 喜田正孝, 水越孝典, 野谷健一, 戸塚靖則, 福田 博
第１５回日本口腔外科学会北日本地方会, 1989年07月, 日本語, 口頭発表（一般）
［国内会議］

口腔機能解剖学研究　　　　　　　　　　　　　　　
北海道大学大学院歯学研究科

口腔機能解剖学/口腔機能形態学　　　　　　　　　　　　　　　
北海道大学大学院歯学研究科

口腔生物学と医学～口腔生物学ー構造、機能と疾患ー　　　　　　　　　　　　　　　
北海道大学大学院歯学研究科

歯学研究概論～動物実験法概論～　　　　　　　　　　　　　　　
北海道大学大学院歯学研究科

歯学研究概論～顕微鏡概論～　　　　　　　　　　　　　　　
北海道大学大学院歯学研究科

組織解析学技法～電子顕微鏡法～　　　　　　　　　　　　　　　
北海道大学大学院歯学研究科

組織解析学技法～光学顕微鏡法～　　　　　　　　　　　　　　　
北海道大学大学院歯学研究科

一般教育演習「唾液のサイエンス～知られざるその能力～」　　　　　　　　　　　　　　　
北海道大学

臨床講義　　　　　　　　　　　　　　　
北海道大学歯学部

統合講義　　　　　　　　　　　　　　　
北海道大学歯学部

全人教育演習　　　　　　　　　　　　　　　
北海道大学歯学部

研究実習　　　　　　　　　　　　　　　
北海道大学歯学部

基本技術実習　　　　　　　　　　　　　　　
北海道大学歯学部

基礎形態学　　　　　　　　　　　　　　　
北海道大学歯学部

解剖学・口腔解剖学　　　　　　　　　　　　　　　
北海道大学歯学部

組織学・口腔組織学実習　　　　　　　　　　　　　　　
北海道大学歯学部

組織学・口腔組織学　　　　　　　　　　　　　　　
北海道大学歯学部

口腔感覚を介する唾液腺機能の維持と再生における神経・内分泌機構とその分子基盤
科学研究費助成事業 基盤研究(C)
2023年04月 - 2026年03月
根津 顕弘
日本学術振興会, 基盤研究(C), 北海道医療大学, 23K09124

複数のスキャホールドを用いた新規空間的ドラッグデリバリーシステムの開発　　　　　　　　　　　　　　　
科学研究費 基盤研究(C)
2016年04月 - 2019年03月
斎藤恵美子
日本学術振興会, 競争的資金

空間的ドラッグデリバリーシステムによる成長因子複合移植法の開発　　　　　　　　　　　　　　　
科学研究費 基盤研究(C)
2013年04月 - 2016年03月
斎藤恵美子
日本学術振興会, 競争的資金

ソフトフード摂取により誘導される唾液腺萎縮のメカニズムの解明　　　　　　　　　　　　　　　
科学研究費 基盤研究（B)
2009年04月 - 2013年03月
髙橋 茂
文部科学省, 研究代表者, 競争的資金

Morphological studies on effcets of soft food on oral tissue　　　　　　　　　　　　　　　
Basic Science Research Program
2009年
競争的資金

未固定・未脱灰切片によるセメント質の石灰化機序についての組織学的研究　　　　　　　　　　　　　　　
科学研究費 基盤研究費（C)（２）
2005年04月 - 2007年03月
山本恒之
文部科学省, 競争的資金

内分泌攪乱物質の唾液腺癌の発生・形質転換への関与と関レセプターの動態への対応　　　　　　　　　　　　　　　
科学研究費 基盤研究（B)（２）
2005年04月 - 2007年03月
向後隆男
文部科学省, 競争的資金

生体硬組織結晶の発現機構と成長に関する三次元超微構造の解明　　　　　　　　　　　　　　　
科学研究費 基盤研究（B)（２）
2003年04月 - 2007年03月
脇田 稔
文部科学省, 競争的資金

緑色蛍光発色核により標識された細胞融合を用いる破骨細胞の延命機構の解析　　　　　　　　　　　　　　　
科学研究費 基盤研究（C)（２）
2004年04月 - 2006年03月
土門卓文
文部科学省, 競争的資金

超高圧電子顕微鏡を用いた生体膜の三次元的超微構造に関する研究　　　　　　　　　　　　　　　
科学研究費 萌芽研究
2003年04月 - 2006年03月
脇田 稔
文部科学省, 競争的資金

唾液腺腺癌の環境ホルモンレセプターの動態解明へのナノチューブ応用のX線的解析　　　　　　　　　　　　　　　
科学研究費 萌芽研究
2003年04月 - 2005年03月
向後隆男
文部科学省, 競争的資金

唾液腺組織再生における細胞増殖と細胞死の意義の解明　　　　　　　　　　　　　　　
科学研究費 基盤研究（C)（２）
2003年04月 - 2005年03月
髙橋 茂
文部科学省, 研究代表者, 競争的資金

内分泌攪乱物質の唾液腺癌の誘発・進展への関与と性ホルモンとVAレセプターの動態　　　　　　　　　　　　　　　
科学研究費 基盤研究（B)（２）
2002年04月 - 2004年03月
向後隆男
文部科学省, 競争的資金

導管障害顎下腺における筋上皮細胞の細胞死と細胞増殖に関する研究　　　　　　　　　　　　　　　
科学研究費 基盤研究（C)(2)
2001年04月 - 2003年03月
髙橋 茂
文部科学省, 研究代表者, 競争的資金

内分泌攪乱物質の唾液腺癌の形態形質転換への影響と性ホルモン・VAレセプターの動態
科学研究費助成事業
2002年 - 2003年
向後 隆男, 進藤 正信, 飯塚 正, 東野 史裕, 高橋 茂
唾液腺腫瘍は、多彩な組織像を示し、病態を多様化し、診断および治療に支障をきたすことが多い。その多彩性の要因の一つとして環境ホルモン(内分泌撹乱物質)に着目し、性ホルモンの影響を誘発唾液腺癌を用い病理組織学的に検索した。
1)DMBA誘発ラット顎下腺癌は、腺房の変性・消失、導管の変化が初期に生じ、その後、小導管の異型増殖を示し腺癌の発生をみた。腺癌の成り立ちには導管上皮や筋上皮の関与があった。正常顎下腺の筋上皮細胞は腺房と介在部導管にみられ、線条部、小葉内分泌導管にはなく、排出導管結紮による萎縮早期の小導管にみられ、太い導管には認められなかった。萎縮晩期では、太い導管の末梢にもみられた。PCNA発現は低値であった。
2)ラットの卵巣非摘出または卵巣摘出(OV)後に顎下腺にDMBAを投与、あるいはDMBA誘発腺癌発育後にOVやtamoxifen投与を行った。雌では腺癌が有意に多発し、OVでは腺癌から扁平上皮癌への形態形質変異が生じ、扁平上皮癌への移行傾向がみられ、移行像では小導管構成様細胞に形質変異を生じた。形態形質転換早期には腺癌構成エストロジェン・レセプター(ER)発現細胞にアポトーシスがみられ、形態形質転換晩期の扁平上皮癌様細胞ではER発現は殆ど消失した。その後、移行した扁平上皮癌の一部に再度ER発現細胞が認められるようになった。
3)精巣摘出(OR)後に顎下腺にDMBAを投与、DMBA投与後にOR、ORあるいはOV後にDMBA投与、DMBA投与後にORあるいはOVを行い発癌後にDiethylstilbestrol投与したもの等では、発癌過程、誘発癌の組織像に相異が種々みられた。類似した組織像でも、サイトケラチン、PCNA、S-100蛋白の発現動態に差異が認められた。
唾液腺癌の多彩な組織像や形態形質転換には性ホルモン、ER発現動態の関与が強く示唆された。
日本学術振興会, 基盤研究(B), 北海道大学, 14370600

唾液腺癌の誘発・組織像・進展への内分泌攪乱物質の関与と性ホルモンレセプターの動態　　　　　　　　　　　　　　　
科学研究費 基盤研究（B)(2)
2000年04月 - 2002年03月
向後隆男
文部科学省, 競争的資金

エナメル質発生の三次元的検索：エナメル質基質の構造と組成の変化　　　　　　　　　　　　　　　
科学研究費 基盤研究（C)
1999年04月 - 2001年03月
脇田 稔
文部科学省, 競争的資金

導管結紮ラット顎下腺における細胞増殖と細胞死に関する形態学的研究　　　　　　　　　　　　　　　
科学研究費 奨励研究（A)
1999年04月 - 2001年03月
髙橋 茂
文部科学省, 研究代表者, 競争的資金

唾液腺癌の実験的誘発および組織像の多彩性に及ぼす性ホルモンとそのレセプターの動態　　　　　　　　　　　　　　　
科学研究費 基盤研究（B)
1998年04月 - 2000年03月
向後隆男
文部科学省, 競争的資金

ラット耳下腺筋上皮細胞の再生に関する研究　　　　　　　　　　　　　　　
科学研究補助金（個人）
1998年04月 - 1999年03月
髙橋 茂
ホクサイテック財団, 研究代表者, 競争的資金

ラット顎下腺筋上皮細胞の再生に関する免疫組織化学的研究　　　　　　　　　　　　　　　
科学研究費 奨励研究（A)
1996年04月 - 1997年03月
髙橋 茂
文部省, 研究代表者, 競争的資金

破骨細胞の多核化機構に関する形態学的研究;単核の破骨細胞の役割とその意義の解明
科学研究費助成事業
1995年 - 1996年
土門 卓文, 飯塚 正, 高橋 茂, 山本 恒之
硬組織を吸収する破歯細胞や破骨細胞は多核の巨細胞として知られている。近年、研究代表者は、波状縁を有する単核の破骨細胞・破歯細胞の存在を報告した。しかしながら、波状縁を持つ単核の破骨細胞・破歯細胞が、どの程度の比率で存在しているのかについては理解されてなく、さらには単核細胞を含む破骨細胞・破歯細胞の核数の分布についてもわかっていない。
材料と方法:6本のヒト乳歯を用い、試料を固定・脱灰後、TRAP活性反応をアゾ色素法で検出した。その後、試料をエポン包埋し、TRAP陽性細胞の連続準超薄切片を作製し、光顕で観察した。準超薄切片上で明らかに吸収窩を形成しているTRAP陽性細胞を選択し、連続切片からそれらの核数を計測した。
結果:連続準超薄切片による観察から、TRAP陽性細胞の多くは多核の細胞であったが、単核の細胞も幾つか観察された。光顕的に、これらTRAP陽性細胞は、歯根象牙質上に吸収窩を形成し、吸収部位に刷子縁striated borderが観察された。このような特徴を持つ242個の細胞を、核数にかかわらず、本研究では破歯細胞とした。吸収窩を形成していた破歯細胞の核数の平均値は5.3、中央値は4、単核の破歯細胞は3%の頻度で存在していた。また、10核以下の核数を持つ破歯細胞は全体の94%を占めていた。
結論:破歯細胞の大部分が10核以下の核を持つ小さな細胞であり、単核の破歯細胞は多核の破歯細胞と共に乳歯歯根吸収に関与することが示唆された。
日本学術振興会, 基盤研究(C), 北海道大学, 07671959

ラット顎下腺再生過程における増殖活性部位の三次元的検索　　　　　　　　　　　　　　　
科学研究費 奨励研究（A)
1994年04月 - 1995年03月
髙橋 茂
文部省, 研究代表者, 競争的資金

培養破骨細胞の移動機構の三次元的解明：微速度撮影法による細胞運動の観察　　　　　　　　　　　　　　　
科学研究費 一般研究（B)
1992年04月 - 1994年03月
脇田 稔
文部省, 競争的資金

Atrophy and regeneration of salivary glands　　　　　　　　　　　　　　　
1988年
競争的資金