解剖学講座 発生生物・再生医学分野

• 講座概要
• 教授挨拶
• スタッフ
• 主な研究
• 主な業績

講座概要

私たちの体は、約270種類・約37兆個もの細胞からなる緻密な社会です。本教室では、人体の構造と機能、特に歯科医師にとって極めて重要な「口腔諸器官」がどのように作られ（発生）、どう機能しているのかを細胞・組織レベルで深く学修します。細胞が組織や器官をかたちづくり、人体を維持する仕組みを理解することは、あらゆる病気の原因や治療法を学ぶ上での強固な土台となります。組織学の講義や基礎配属実習を通じて、臨床へとつながる確かな基礎知識を一緒に身につけていきましょう。

教授挨拶

エナメル質は、生体の中で最も硬い組織です。なぜ、このように硬く美しい組織が形成されるのでしょうか。その問いは、私たちが長年追い続けてきた研究テーマです。

私たちは、エナメル質を形成するエナメル上皮幹細胞の存在を明らかにするとともに、その幹細胞を維持する「幹細胞ニッチ」の役割を解明してきました。さらに、幹細胞からエナメル芽細胞への分化機構や、エナメル質が石灰化していく仕組みについて研究を進めています。これらの研究は、エナメル質形成不全症をはじめとする疾患の病因や病態の解明にもつながっています。

最近の研究では、エナメル上皮細胞はエナメル質を形成するだけでなく、形成後も歯を守る重要な役割を担っていることを明らかにしました。私たちは、こうしたエナメル質形成のメカニズムを解き明かすことで、歯の健康を生涯にわたって守り、人々が「おいしく食べる」という当たり前の喜びを支えるとともに、Well-beingの実現に貢献したいと考えています。

エナメル質研究を基盤として、次世代の歯科医療と再生医療を切り拓くこと。それが私たちの目指す研究です。

講座スタッフ

教授	原田　英光	はらだ　ひでみつ
特任教授	大津　圭史	おおつ　けいし
講師	池崎　晶二郎	いけざき　しょうじろう
大学院生	小原　康輔	おばら　こうすけ

講座における主たる研究テーマ

• エナメル上皮幹細胞ニッチの維持と細胞分化機構の解明
• エナメル質石灰化における分子生物学的メカニズムの解明とエナメル質形成不全症の病因・病態の解明
• 接合上皮のバリア機能メカニズムとその破綻による歯周病発症との関連性の追求
• ヘルトビッヒ上皮鞘による歯根発生メカニズムと歯原性腫瘍の発症・病態との関連性の追求

講座の主な業績

【令和7（2025）年度】

1. Otsu K, Ikezaki S, Goto-Matsumoto N, Ikarashi A, Sano H, Ida-Yonemochi H, et al. V-ATPase a3 Directs Secretory Lysosome Transport in Enamel Formation. J Dent Res. 2026;105(9):1195-1204. doi: 10.1177/00220345251401512.
2. Lee JM, Ha YS, Lee SJ, Kim HY, Adpaikar AA, Kim EJ, et al. RUNX2 enhances vascular remodeling to promote endothelial proliferation in acute liver injury. Int J Biol Sci. 2026;22(7):3909-3924. doi: 10.7150/ijbs.123366.
3. Takaman M, Otsu K, Ikezaki S, Noda M, Harada H. Odontogenic ameloblast-associated protein (ODAM)-enriched coating improves adhesion of junctional epithelial cells to composite resin via AKT activation. J Oral Biosci. 2026;68(1):100725. doi: 10.1016/j.job.2025.100725.
4. Shindo Y, Ikezaki S, Iwayama T, Otsu K, Kido Y, Kakura K, et al. Basement Membrane of Hertwig’s Epithelial Root Sheath Is Involved in Dental Follicle Cell Differentiation into Cementoblasts. Stem Cells Dev. 2026;35(1-2):13-22. doi: 10.1177/15473287251400301.

【令和6（2024）年度】

1. 1. Shimamura K, Nojiri T, Kondo H, Ikeda Y, Yasuhara R, Ida-Yonemochi H, et al. The potential role of chromodomain helicase DNA-binding protein 3 in defining the cervical width by regulating the early growth stage of the apical papilla during tooth development. J Oral Biosci. 2025;67(1):100604. doi: 10.1016/j.job.2024.100604.
2. 2.Ikeda Y, Yasuhara R, Tanaka J, Ida-Yonemochi H, Akiyama H, Otsu K, et al. PLAG1 overexpression in salivary gland duct-acinar units results in epithelial tumors with acinar-like features: Tumorization of luminal stem/progenitor cells may result in the development of salivary gland tumors consisting of only luminal cells. J Oral Biosci. 2024;66(4):88-97. doi: 10.1016/j.job.2024.08.002.

【令和5（2023）年度】

1. Ida-Yonemochi H, Otsu K, Irié T, Ohazama A, Harada H, Ohshima H. Loss of Autophagy Disrupts Stemness of Ameloblast-Lineage Cells in Aging. J Dent Res. 2024;103(2):156-166. doi: 10.1177/00220345231209931.
2. Shin M, Matsushima A, Nagao JI, Tanaka Y, Harada H, Okabe K, et al. Mobility gene expression differences among wild-type, Mmp20 null and Mmp20 over-expresser mice plus visualization of 3D mouse ameloblast directional movement. Sci Rep. 2023;13(1):18829. doi: 10.1038/s41598-023-44627-0.

【令和4（2022）年度】

1. Ikezaki S, Otsu K, Kumakami-Sakano M, Harada H. A novel junctional epithelial cell line, mHAT-JE01, derived from incisor epithelial cells. J Oral Biosci. 2023;65(1):47-54. doi: 10.1016/j.job.2023.01.004.
2. Azumane M, Ikezaki S, Otsu K, Kumakami-Sakano M, Arai H, Yamada H, et al. Semaphorin-RhoA signaling regulates HERS maintenance by acting against TGF-β-induced EMT. J Periodontal Res. 2023;58(1):184-194. doi: 10.1111/jre.13080.
3. Li S, Lee DJ, Kim HY, Harada H, Jung YS, Jung HS. Transcriptomic Comparison Analysis between Ameloblastoma and AM-1 Cell Line. Int J Stem Cells. 2022;15(4):415-421. doi: 10.15283/ijsc22132.
4. Li S, Kim HY, Lee DJ, Park SH, Otsu K, Harada H, et al. Inhibition of L-type voltage-gated calcium channel-mediated Ca²+ influx suppresses the collective migration and invasion of ameloblastoma. Cell Prolif. 2022;55(11):e13305. doi: 10.1111/cpr.13305.
5. Arai H, Inaba A, Ikezaki S, Kumakami-Sakano M, Azumane M, Ohshima H, et al. Energy metabolic shift contributes to the phenotype modulation of maturation stage ameloblasts. Front Physiol. 2022;13:1062042. doi: 10.3389/fphys.2022.1062042.
6. Morita W, Morimoto N, Otsu K, Miura T. Stripe and spot selection in cusp patterning of mammalian molar formation. Sci Rep. 2022;12(1):9149. doi: 10.1038/s41598-022-13539-w.

【令和3（2021）年度】

1. Inaba A, Harada H, Ikezaki S, Kumakami-Sakano M, Arai H, Azumane M, et al. LPA6-RhoA signals regulate junctional complexes for polarity and morphology establishment of maturation stage ameloblasts. J Oral Biosci. 2022;64(1):85-92. doi: 10.1016/j.job.2022.01.004.
2. Yang S, Choi H, Kim TH, Jeong JK, Liu Y, Harada H, et al. Cell dynamics in Hertwig’s epithelial root sheath are regulated by β-catenin activity during tooth root development. J Cell Physiol. 2021;236(7):5387-5398. doi: 10.1002/jcp.30243.
3. Mishima S, Takahashi K, Kiso H, Murashima-Suginami A, Tokita Y, Jo JI, et al. Local application of Usag-1 siRNA can promote tooth regeneration in Runx2-deficient mice. Sci Rep. 2021;11(1):13674. doi: 10.1038/s41598-021-93256-y.
4. Kim HY, Li S, Lee DJ, Park JH, Muramatsu T, Harada H, et al. Activation of Wnt signalling reduces the population of cancer stem cells in ameloblastoma. Cell Prolif. 2021;54(7):e13073. doi: 10.1111/cpr.13073.
5. Nishiya N, Oku Y, Ishikawa C, Fukuda T, Dan S, Mashima T, et al. Lamellarin 14, a derivative of marine alkaloids, inhibits the T790M/C797S mutant epidermal growth factor receptor. Cancer Sci. 2021;112(5):1963-1974. doi: 10.1111/cas.14839.
6. Lee SJ, Park J, Lee DJ, Otsu K, Kim P, Mizuno S, et al. Mast4 knockout shows the regulation of spermatogonial stem cell self-renewal via the FGF2/ERM pathway. Cell Death Differ. 2021;28(5):1441-1454. doi: 10.1038/s41418-020-00670-2.

【令和2（2020）年度】

1. Otsu K, Ida-Yonemochi H, Ikezaki S, Ema M, Hitomi J, Ohshima H, et al. Oxygen regulates epithelial stem cell proliferation via RhoA-actomyosin-YAP/TAZ signal in mouse incisor. Development. 2021;148(4):dev194787. doi: 10.1242/dev.194787.
2. Ishiguro S, Shinada T, Wu Z, Karimazawa M, Uchidate M, Nishimura E, et al. A novel cyclic peptide (Naturido) modulates glia-neuron interactions in vitro and reverses ageing-related deficits in senescence-accelerated mice. PLoS One. 2021;16(1):e0245235. doi: 10.1371/journal.pone.0245235.
3. Hino R, Yamada A, Chiba Y, Yoshizaki K, Fukumoto E, Iwamoto T, et al. Melnick-Needles syndrome associated molecule, Filamin-A regulates dental epithelial cell migration and root formation. Pediatr Dent J. 2020;30(3):208-214. doi: 10.1016/j.pdj.2020.09.003.
4. Ida-Yonemochi H, Otsu K, Harada H, Ohshima H. Functional Expression of Sodium-Dependent Glucose Transporter in Amelogenesis. J Dent Res. 2020;99(8):977-986. doi: 10.1177/0022034520916130.

【令和元（2019）年度】

1. Wu Z, Rao Y, Zhang S, Kim EJ, Oki S, Harada H, et al. Cis-control of Six1 expression in neural crest cells during craniofacial development. Dev Dyn. 2019;248(12):1264-1272. doi: 10.1002/dvdy.109.
2. Jimenez-Rojo L, Pagella P, Harada H, Mitsiadis T. Dental Epithelial Stem Cells as a Source for Mammary Gland Regeneration and Milk Producing Cells In Vivo. Cells. 2019;8(10):1302. doi: 10.3390/cells8101302.

【平成30（2018）年度】

1. Kim EJ, Yoon KS, Arakaki M, Otsu K, Fukumoto S, Harada H, et al. Effective Differentiation of Induced Pluripotent Stem Cells Into Dental Cells. Dev Dyn. 2019;248(1):129-139. doi: 10.1002/dvdy.24663.

【平成29（2017）年度】

1. Saito K, Takahashi K, Huang B, Asahara M, Kiso H, Togo Y, et al. Loss of Stemness, EMT, and Supernumerary Tooth Formation in Cebpb-/-Runx2+/- Murine Incisors. Sci Rep. 2018;8(1):5169. doi: 10.1038/s41598-018-23515-y.
2. Kikuchi K, Masuda T, Fujiwara N, Kuji A, Miura H, Jung HS, et al. Craniofacial Bone Regeneration using iPS Cell-Derived Neural Crest Like Cells. J Hard Tissue Biol. 2018;27(1):1-10. doi: 10.2485/jhtb.27.1.
3. Rácz R, Földes A, Bori E, Zsembery Á, Harada H, Steward MC, et al. No Change in Bicarbonate Transport but Tight-Junction Formation Is Delayed by Fluoride in a Novel Ameloblast Model. Front Physiol. 2017;8:940. doi: 10.3389/fphys.2017.00940.

【平成28（2016）年度】

1. Itaya S, Oka K, Ogata K, Tamura S, Kira -Tatsuoka M, Fujiwara N, et al. Hertwig’s epithelial root sheath cells contribute to formation of periodontal ligament through epithelial-mesenchymal transition by TGF-β. Biomed Res (Tokyo). 2017;38(1):61-69. doi: 10.2220/biomedres.38.61.
2. Nakamura T, Chiba Y, Naruse M, Saito K, Harada H, Fukumoto S. Globoside accelerates the differentiation of dental epithelial cells into ameloblasts. Int J Oral Sci. 2016;8(4):205-212. doi: 10.1038/ijos.2016.35.
3. Otsu K, Ida-Yonemochi H, Fujiwara N, Harada H. The Semaphorin 4D-RhoA-Akt Signal Cascade Regulates Enamel Matrix Secretion in Coordination with Cell Polarization During Ameloblast Differentiation. J Bone Miner Res. 2016;31(11):1943-1954. doi: 10.1002/jbmr.2876.
4. Togo Y, Takahashi K, Saito K, Kiso H, Tsukamoto H, Huang B, et al. Antagonistic Functions of USAG-1 and RUNX2 during Tooth Development. PLoS One. 2016;11(8):e0161067. doi: 10.1371/journal.pone.0161067.
5. Lee MJ, Kim EJ, Otsu K, Harada H, Jung HS. Sox2 contributes to tooth development via Wnt signaling. Cell Tissue Res. 2016;365(1):77-84. doi: 10.1007/s00441-016-2363-4.
6. Otsu K, Harada H. Rho GTPases in ameloblast differentiation. Jpn Dent Sci Rev. 2016;52(2):32-40. doi: 10.1016/j.jdsr.2015.09.001.
7. Bori E, Guo J, Rácz R, Burghardt B, Földes A, Kerémi B, et al. Evidence for Bicarbonate Secretion by Ameloblasts in a Novel Cellular Model. J Dent Res. 2016;95(5):588-596. doi: 10.1177/0022034515625939.

【平成27（2015）年度】

1. Ida-Yonemochi H, Otsu K, Ohshima H, Harada H. The glycogen metabolism via Akt signaling is important for the secretion of enamel matrix in tooth development. Mech Dev. 2016;139:18-30. doi: 10.1016/j.mod.2016.01.002.
2. Yokohama-Tamaki T, Otsu K, Harada H, Shibata S, Obara N, Irie K, et al. CXCR4/CXCL12 signaling impacts enamel progenitor cell proliferation and motility in the dental stem cell niche. Cell Tissue Res. 2015;362(3):633-642. doi: 10.1007/s00441-015-2248-y.
3. Nakatomi C, Nakatomi M, Saito K, Harada H, Ohshima H. The enamel knot-like structure is eternally maintained in the apical bud of postnatal mouse incisors. Arch Oral Biol. 2015;60(8):1122-1130. doi: 10.1016/j.archoralbio.2015.05.001.
4. Harada H, Kumakami-Sakano M, Fujiwara N, Otsu K. Live imaging to elucidate cell dynamics in tooth organogenesis and regeneration. J Oral Biosci. 2015;57(2):65-68. doi: 10.1016/j.job.2015.02.005.

【平成26（2014）年度】

1. Mitsiadis TA, Harada H. Regenerated Teeth: The Future of Tooth Replacement. An Update. Regen Med. 2015;10(1):5-8. doi: 10.2217/rme.14.78.
2. Masuda T, Otsu K, Kumakami-Sakano M, Fujiwara N, Ema M, Hitomi J, et al. Combined Administration of BMP-2 and HGF Facilitate Bone Regeneration through Angiogenic Mechanisms. J Hard Tissue Biol. 2015;24(1):7-16. doi: 10.2485/jhtb.24.7.
3. Kumakami-Sakano M, Otsu K, Fujiwara N, Harada H. Regulatory mechanisms of Hertwig’s epithelial root sheath formation and anomaly correlated with root length. Exp Cell Res. 2014;325(2):78-82. doi: 10.1016/j.yexcr.2014.02.005.

【平成25（2013）年度】

1. Otsu K, Kumakami-Sakano M, Fujiwara N, Kikuchi K, Keller L, Lesot H, et al. Stem cell sources for tooth regeneration: current status and future prospects. Front Physiol. 2014;5:36. doi: 10.3389/fphys.2014.00036.
2. Ida-Yonemochi H, Harada H, Ohshima H, Saku T. Reciprocal expressions between α-dystroglycan and integrin β1, perlecan receptors, in the murine enamel organ development. Gene Expr Patterns. 2013;13(8):293-302. doi: 10.1016/j.gep.2013.05.004.
3. Otsu K, Sakano M, Masuda T, Fujiwara N, Harada H. The role of Rho-kinases in ameloblast differentiation. J Oral Biosci. 2013;55(4):159-164. doi: 10.1016/j.job.2013.07.001.
4. Arakaki M, Egusa H, Otsu K, Saitoh I, Miura T, Harada H. Frontier dental research on iPS cells. J Oral Biosci. 2013;55(4):191-199. doi: 10.1016/j.job.2013.08.002.
5. Koizumi Y, Kawashima N, Yamamoto M, Takimoto K, Zhou M, Suzuki N, et al. Wnt11 expression in rat dental pulp and promotional effects of Wnt signaling on odontoblast differentiation. Congenit Anom (Kyoto). 2013;53(3):101-108. doi: 10.1111/cga.12011.
6. Zheng L, Seon YJ, Mourão MA, Schnell S, Kim D, Harada H, et al. Circadian rhythms regulate amelogenesis. Bone. 2013;55(1):158-165. doi: 10.1016/j.bone.2013.02.011.
7. Jedeon K, De la Dure-Molla M, Brookes SJ, Loiodice S, Marciano C, Kirkham J, et al. Enamel Defects Reflect Perinatal Exposure to Bisphenol A. Am J Pathol. 2013;183(1):108-118. doi: 10.1016/j.ajpath.2013.04.004.
8. Ishihata K, Kume K, Hijioka H, Kibe T, Tanaka S, Komatsuzawa H, et al. Expression of antimicrobial peptides and E-cadherin in periapical lesions. Oral Sci Int. 2013;10(2):70-76. doi: 10.1016/s1348-8643(13)00004-9.
9. Sakano M, Otsu K, Fujiwara N, Fukumoto S, Yamada A, Harada H. Cell dynamics in cervical loop epithelium during transition from crown to root: implications for Hertwig’s epithelial root sheath formation. J Periodontal Res. 2013;48(2):262-267. doi: 10.1111/jre.12003.

【平成24（2012）年度】

1. Chavez MG, Yu W, Biehs B, Harada H, Snead ML, Lee JS, et al. Characterization of Dental Epithelial Stem Cells from the Mouse Incisor with Two-Dimensional and Three-Dimensional Platforms. Tissue Eng Part C Methods. 2013;19(1):15-24. doi: 10.1089/ten.tec.2012.0232.