Epiprofin regulation in cell proliferation and differentiation in tooth development

• Project/Area Number: 15H05032
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dental engineering/Regenerative dentistry
• Research Institution: Tohoku University
• Principal Investigator: Nakamura Takashi 東北大学, 歯学研究科, 准教授 (90585324)
• Co-Investigator(Kenkyū-buntansha): 福本 敏 東北大学, 歯学研究科, 教授 (30264253) ; 江草 宏 東北大学, 歯学研究科, 教授 (30379078)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2016: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2015: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
• Keywords: エナメル芽細胞 / 転写因子 / エピプロフィン / 歯の再生 / エナメル / 歯原性上皮細胞 / 再生医療 / 幹細胞 / 器官形成 / 歯の発生 / 細胞分化 / 運命決定 / 上皮 / 増殖 / 細胞周期 / 分化

Outline of Final Research Achievements

We previously identified Epiprofin(Epfn) as a novel member of Sp transcription factor family that is expressed in certain ectodermal organs, such as teeth, hair follicles, nails and skin. During tooth development, Epfn regulates cell proliferation as well as cell migration at the early stages and cell differentiation in the later mature stage by controlling the phosphorylation of Epfn. We also identified a small molecule that strongly induced the expression of Epfn in dental epithelial cells. We are applying the Epfn -inducible small molecule in enamel biosynthesis of regenerative dentistry.

Research Products

• [Int'l Joint Research] NIDCR, NIH(米国)
• [Int'l Joint Research] University of the Basque Country(Spain)
• [Int'l Joint Research] Peking University(中国)
• [Int'l Joint Research] Yonsei University(韓国)
• [Journal Article] Epiprofin Regulates Enamel Formation and Tooth Morphogenesis by Controlling Epithelial-Mesenchymal Interactions During Tooth Development. (2017)
  • Author(s): Nakamura T, Jimenez-Rojo L, Koyama E, Pacifici M, de Vega S, Iwamoto M, Fukumoto S, Unda F, Yamada Y.
  • Journal Title: J Bone Miner Res. Volume: 32 Issue: 3 Pages: 601-610
  • DOI: 10.1002/jbmr.3024
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Pannexin 3 regulates proliferation and differentiation of odontoblasts via its hemichannel activities (2017)
  • Author(s): Iwamoto Tsutomu、Nakamura Takashi、Ishikawa Masaki、Yoshizaki Keigo、Sugimoto Asuna、Ida-Yonemochi Hiroko、Ohshima Hayato、Saito Masahiro、Yamada Yoshihiko、Fukumoto Satoshi
  • Journal Title: PLOS ONE Volume: 12 Issue: 5 Pages: 0177557-0177557
  • DOI: 10.1371/journal.pone.0177557
  • NAID: 120006534958
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Globoside accelerates the differentiation of dental epithelial cells into ameloblasts (2016)
  • Author(s): Nakamura, T., Chiba, Y., Naruse, M., Harada, H., and Fukumoto, S.
  • Journal Title: Intenational Journal of Oral Science Volume: 8(4) Issue: 4 Pages: 205-212
  • DOI: 10.1038/ijos.2016.35
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Wnt/β-Catenin Regulates the Activity of Epiprofin/Sp6, SHH, FGF, and BMP to Coordinate the Stages of Odontogenesis. (2016)
  • Author(s): Aurrekoetxea, M., Irastorza, I., García-Gallastegui, P., Jiménez-Rojo, R., Nakamura, T., Yamada, Y., Ibarretxe, G., and Unda, F.
  • Journal Title: Frontiers in Cell and Developmental Biology Volume: in press Pages: 4-25
  • DOI: 10.3389/fcell.2016.00025
  • Peer Reviewed / Open Access
• [Journal Article] Fine tuning of Rac1 and RhoA alters cuspal shapes by remolding the cellular geometry (2016)
  • Author(s): Li, L., Tang, Q., Nakamura, T., Suh, JG., Ohshima, H., and Jung, HS.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 37828-37828
  • DOI: 10.1038/srep37828
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A 3D culture model study monitoring differentiation of dental epithelial cells into ameloblast-like cells (2016)
  • Author(s): Tadaki, M., Anada, T., Shiwaku, Y., Nakamura, T., Nakamura, M., Kojima, M., Arai, T., Fukumoto, S., and Suzuki, O.
  • Journal Title: RSC Advances Volume: 6(67) Issue: 67 Pages: 62109-62109
  • DOI: 10.1039/c6ra04570g
  • Peer Reviewed
• [Journal Article] A p38 MAP kinase is required for Wnt3a-mediated osterix expression independently of Wnt-LRP5/6-GSK3β signaling axis in dental follicle cells (2016)
  • Author(s): Sakisaka, Y., Kanaya, S., Nakamura, T., Tamura, M., Shimauchi, H., and Nemoto, E.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 478(2) Issue: 2 Pages: 527-532
  • DOI: 10.1016/j.bbrc.2016.07.076
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Connexin 43 is necessary for salivary gland branching morphogenesis and FGF10-induced ERK1/2 phosphorylation (2016)
  • Author(s): Yamada A, Futagi M, Fukumoto E, Saito K, Yoshizaki K, Ishikawa M, Arakaki M, Hino R, Sugawara Y, Ishikawa M, Naruse M, Miyazaki K, Nakamura T, Fukumoto S.
  • Journal Title: The Journal of Biological Chemistry Volume: 291 Issue: 2 Pages: 904-912
  • DOI: 10.1074/jbc.m115.674663
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Interaction between Fibronectin and β1 Integrin is Essential for Tooth Development. (2015)
  • Author(s): Saito, K., Fukumoto, E., Yamada, A., Yuasa, K., Yoshizaki, K., Iwamoto, T., Saito, M., Nakamura, T., and Fukumoto, S.
  • Journal Title: PLOS one Volume: 10(4)
  • NAID: 120006872347
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Wnt3a signaling induces murine dental follicle cells to differentiate into cementoblastic/osteoblastic cells via an osterix-dependent pathway. (2015)
  • Author(s): Nemoto, E., Sakisaka, M., Tsuchiya, M., Tamura, M., Nakamura, T., Shimonishi, M., and Shimauchi
  • Journal Title: Journal of Periodontal Research Volume: 51(2) Issue: 2 Pages: 164-174
  • DOI: 10.1111/jre.12294
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Wnt5a attenuates canonical Wnt-induced alkaline phosphatase expression in dental follicle cells. (2015)
  • Author(s): Sakisaka, Y., Tsuchiya, M., Nakamura, T., Tamura, M., Shimauchi, H., and Nemoto, E.
  • Journal Title: Experimental Cell Research Volume: 336(1) Issue: 1 Pages: 85-93
  • DOI: 10.1016/j.yexcr.2015.06.013
  • Peer Reviewed
• [Presentation] Zn2+ Hyperpolarizes Osteoblastic MC3T3-E1 Cells by Activating IK and BK Channels (2017)
  • Author(s): Mengkai Guang, Takashi Yoshida, Takashi Nakamura, Ping Gong, Minoru Wakamori
  • Organizer: 95th General Session & Exhibition of the IADR
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2017-03-22
  • Int'l Joint Research
• [Presentation] Zn2+ Hyperpolarizes Osteoblastic MC3T3-E1 Cells by Activating IK and BK Channels (2017)
  • Author(s): Mengkai Guang, Takashi Yoshida, Takashi Nakamura, Ping Gong, Minoru Wakamori,
  • Organizer: 95th General Session & Exhibition of the IADR
  • Int'l Joint Research
• [Presentation] エピプロフィンによる骨代謝調節 (2016)
  • Author(s): 中村 卓史，中村 友昭，若森 実，福本 敏
  • Organizer: 第58回歯科基礎医学会・学術大会
  • Place of Presentation: 札幌
  • Year and Date: 2016-08-24
• [Presentation] Transcriptional regulation of Epiprofin (2016)
  • Author(s): Takashi Nakamura
  • Organizer: TMD 2016
  • Place of Presentation: Porvoo, Finland
  • Year and Date: 2016-06-13
  • Int'l Joint Research
• [Presentation] 白血病治療を目的としたヒト乳歯歯髄細胞からの人工骨髄誘導法の開発 (2015)
  • Author(s): 山田亜矢、菊入宗、中村卓史、新垣真紀子、齋藤幹、福本敏
  • Organizer: 第５３回日本小児歯科学会大会
  • Place of Presentation: 広島
  • Year and Date: 2015-05-21
• [Presentation] 歯の萌出時期と嚢胞形成に関わるインテグリンbeta1の分子機構について (2015)
  • Author(s): 齋藤幹、山田亜矢、新垣真紀子、二木正晴、中村卓史、福本敏
  • Organizer: 第５３回日本小児歯科学会大会
  • Place of Presentation: 広島
  • Year and Date: 2015-05-21
• [Book] 口腔機能のアンチエイジング 1. 発生から考えた歯の再生 (2015)
  • Author(s): 福本 敏、新垣真紀子、山田亜矢、齋藤 幹、中村卓史
  • Publisher: メディカルビュー社
• [Book] エナメル芽細胞の分化制御機構 (2015)
  • Author(s): 中村卓史
  • Publisher: 臨床医学出版