Elucidate the regulational mechanism of tooth bud formation

• Project/Area Number: 24390441
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• 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(研究院), 准教授 (90585324)
• Co-Investigator(Kenkyū-buntansha): SAKAI Takayoshi 大阪大学, 歯学研究科(大学院), 教授 (90379082) ; SAITO Masahiro 東北大学, 歯学研究科(大学院), 教授 (40215562)
• Co-Investigator(Renkei-kenkyūsha): FUKUMOTO Satoshi 東北大学, 歯学研究科(大学院), 教授 (30264253)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2014: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2013: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
• Keywords: 歯 / 上皮 / エピプロフィン / 細胞増殖 / Transit Amplifying cells / Notch / 運命決定 / 分化 / エナメル芽細胞 / ケラチノサイト / 細胞周期 / 細胞分化 / 転写制御 / 上皮系器官 / 歯の発生 / 歯原性上皮細胞 / 転写因子 / Wntシグナル

Outline of Final Research Achievements

The final goal of this study is to elucidate the molecular mechanism of the regulation in the number of teeth by novel transcription factor Epiprofin in tooth germ formation and development. Our analysis of Epfn KO mice revealed that Epiprofin promotes the transitory cell proliferative activities in keratinocyte as well as dental epithelial cells. In Epfn KO mice, keratinocytes and dental epithelial cells keep migrating into dental mesenchyme due to the decrease of proliferation activity and apoptosis of cells. In addition, Epfn contributes to activate the cell proliferation of Transit Amplifying cells produced from stem cells through Notch signaling. Furthermore Epfn exerts a critical role in cell fate determination of dental epithelial cells and epithelial stem cells.

Research Products

• [Journal Article] Novel Hedgehog Agonists Promote Osteoblast Differentiation in Mesenchymal Stem Cells (2015)
  • Author(s): Takashi Nakamura, Masahiro Naruse, Yuta Chiba, Toshihisa Komori, Keiichi Sasaki, Masahiro Iwamoto, Satoshi Fukumoto
  • Journal Title: Journal of Cellular Physiology Volume: 230(4) Issue: 4 Pages: 922-929
  • DOI: 10.1002/jcp.24823
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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) Issue: 4 Pages: 1-12
  • DOI: 10.1371/journal.pone.0121667
  • NAID: 120006872347
  • Peer Reviewed / Open Access
• [Journal Article] Epiprofin orchestrates epidermal keratinocyte proliferation and differentiation. (2014)
  • Author(s): Nakamura, T., Yoshitomi, Y., Patel, V., Fukumoto, S., and Yamada, Y.
  • Journal Title: Journal of cell science Volume: 127(24) Pages: 5261-5272
  • DOI: 10.1242/jcs.156778
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Establishment of ex vivo mucocele model using salivary gland organ culture. (2014)
  • Author(s): Hino, R., Futagi, M., Yamada, A., Arakaki, M., Saito, K., Sugawara, Y., Ono, M., Fukumoto, E., Nakamura, T., and Fukumoto, S.
  • Journal Title: Pediatric dental journal Volume: 24(2) Issue: 2 Pages: 78-82
  • DOI: 10.1016/j.pdj.2014.03.003
  • Peer Reviewed / Open Access
• [Journal Article] A vitamin D3 analog augmented interleukin-8 production by human monocytic cells in response to various microbe-related synthetic ligands, especially NOD2 agonistic muramyldipeptide (2013)
  • Author(s): Ikeuchi, T., Nakamura, T., Fukumoto, S., and Takada, H.
  • Journal Title: International Immunopharmacology Volume: 15(1) Issue: 1 Pages: 15-22
  • DOI: 10.1016/j.intimp.2012.10.027
  • Peer Reviewed
• [Journal Article] Wnt5a signaling is a substantial constituent in bone morphogenetic protein-2-mediated osteoblastogenesis (2012)
  • Author(s): Nemoto E, Ebe Y, Kanaya S, Tsuchiya M, Nakamura T, Tamura M, Shimauchi H
  • Journal Title: Biochem Biophys Res Commun Volume: 422(4) Issue: 4 Pages: 627-632
  • DOI: 10.1016/j.bbrc.2012.05.039
  • Peer Reviewed
• [Journal Article] Epiprofin/Sp6 regulates mesenchymal Wnt-BMP signaling, and the establishment of cellular junctions during the bell stage of tooth development (2012)
  • Author(s): Ibarretxe, G., Aurrekoetxea, M., Crende, O., Badiola, I., Jimenez-Rojo, L., Nakamura, T., Yamada, Y., and Unda, F.
  • Journal Title: Cell and Tissue Research Volume: 350(1) Issue: 1 Pages: 95-107
  • DOI: 10.1007/s00441-012-1459-8
  • Peer Reviewed
• [Presentation] Molecular mechanism of Epiprofin in epithelial cell proliferation (2014)
  • Author(s): 中村卓史、福本 敏
  • Organizer: 第56回歯科基礎医学会学術大会・総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Regulation of PTH production in parathyroid gland by transcription factor Epiprofin (2014)
  • Author(s): Nakamura, T., Nakashima, N., Pacifici, M., Itoi, K., Yamada, Y., Fukumoto, S., and Iwamoto, M.
  • Organizer: NIH-Japan-JSPS Symposium

  • Place of Presentation: Bethesda, MD
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] FGF-2-Dependent Neurogenesis Is Reduced in Aged Mice and in the Perlecan-Deficient Subventricular Zone of Adult Mice (2014)
  • Author(s): Yamada, T., Kerever, A., Nakamura, T., Yamada, Y., and Arikawa-Hirasawa, E.
  • Organizer: NIH-Japan-JSPS Symposium

  • Place of Presentation: Bethesda, MD
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Mst1/2 regulate dental epithelium proliferation and ameloblast differentiation, (2014)
  • Author(s): Futaki, M., Saito, K., Nakamura, T., Yamada, A., and Fukumoto, S.
  • Organizer: 92nd IADR General Session and Exhibition
  • Place of Presentation: Cape Town, South Africa
  • Year and Date: 2014-06-25 – 2014-06-28
• [Presentation] Novel smoothened agonists promote osteoblast differentiation in C3H10T1/2 cells and osteoblastic cells from Runx2-deficient mice (2014)
  • Author(s): Takashi Nakamura
  • Organizer: International Symposium on Biomaterialization
  • Place of Presentation: Gwangju, Korea
  • Year and Date: 2014-06-14
  • Invited
• [Presentation] 歯髄幹細胞分化における細胞内シグナル制御機構の解明 (2014)
  • Author(s): 菅原 優、岩本勉、小野真理子、新垣真紀子、中村卓史、福本 敏
  • Organizer: 第５２回日本小児歯科学会大会
  • Place of Presentation: 東京
  • Year and Date: 2014-05-16 – 2014-05-17
• [Presentation] アメロブラスチン受容体グリピカン１の歯胚発生過程における発現とその機能解析 (2014)
  • Author(s): 浦川麻衣子、二木正晴、只木麻夕、齋藤幹、中村卓史、福本 敏
  • Organizer: 第５２回日本小児歯科学会大会
  • Place of Presentation: 東京
  • Year and Date: 2014-05-16 – 2014-05-17
• [Presentation] Roles of Epiprofin in tooth development (2013)
  • Author(s): Takashi Nakamura, Satoshi Fukumoto, Lucia Jimenez, Susan de Vega, Fernando Unda, and Yoshihiko Yamada
  • Organizer: 11th International Conference on Tooth Morphogenesis and Differentiation
  • Place of Presentation: フランス （ラロンデ）
• [Presentation] 副甲状腺における新規転写因子エピプロフィンの役割 (2013)
  • Author(s): 中村 卓史
  • Organizer: 第８６回日本内分泌学会学術総会
  • Place of Presentation: 仙台
  • Invited
• [Presentation] Novel Compounds Mimic Hedgehog Activity and Promote Osteoblast Differentiation in C3H10T1/2 Cells and Osteoblastic Cells from Runx2-Deficient Mice (2013)
  • Author(s): Takashi Nakamura, Masahiro Naruse, Tomoko Ikeuchi, Toshihisa Komori, Aya Yamada, Masahiro Iwamoto, and Satoshi Fukumoto
  • Organizer: 2013 American association for Bone and Mineral Research
  • Place of Presentation: アメリカ（ボルティモア）
• [Presentation] Novel Hedgehog Agonists Regulate Dental Epithelial Cell Proliferation and Differentiation (2013)
  • Author(s): Masahiro Naruse, Tomoko Ikeuchi, Yuta Chiba, Satoshi Fukumoto, and Takashi Nakamura
  • Organizer: 2013 American association for Bone and Mineral Research
  • Place of Presentation: アメリカ（ボルティモア）
• [Presentation] 乳歯歯髄を用いた再生医療における課題について (2012)
  • Author(s): 二木かおり、山田亜矢、新垣真紀子、岩本勉、中村卓史、福本 敏
  • Organizer: 第31回小児歯科学会中部地方会
  • Place of Presentation: 金沢
  • Year and Date: 2012-11-25
• [Presentation] 歯科再生利用実現化を目指した新しい分子機能予測法開発 (2012)
  • Author(s): 及川友子、只木麻友、成瀬正啓、新垣真紀子、岩本勉、山田亜矢、中村卓史、福本敏
  • Organizer: 第31回小児歯科学会中四国地方会
  • Place of Presentation: 高松
  • Year and Date: 2012-11-04
• [Presentation] フィラミンAによる歯根形成メカニズムの解析 (2012)
  • Author(s): 宮本 綾子、山田亜矢、岩本勉、中村卓史、福本敏
  • Organizer: 第50回小児歯科学会学術大会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-05-12
• [Presentation] エナメル芽細胞分化過程におけるテトラスパニンCD9の発現 (2012)
  • Author(s): 岩本勉、小野真理子、二木正晴、菅原優、山田亜矢、中村卓史、福本敏
  • Organizer: 第50回小児歯科学会学術大会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-05-12
• [Presentation] Pannexin 3, a Gap Junction Protein, Regulates Proliferation through AMPK Pathway in Odontoblasts (2012)
  • Author(s): T.Iwamoto, M. Ishikawa, K. Yoshizaki, T. Nakamura, A. Yamada, Y. Yamada and S. Fukumoto.
  • Organizer: The American Society For Biochemistry and Molecular Biology
  • Place of Presentation: San Diego, USA
• [Presentation] Pannexin 3, a gap junction protein, regulates odontoblast differentiation (2012)
  • Author(s): Iwamoto, T., Ishikawa, M., Yoshizaki, K., Yamada, A., Nakamura, T., Yamada
  • Organizer: The American Society For Biochemistry and Molecular Biology
  • Place of Presentation: Iguacu Falls, Brazil
• [Presentation] 歯の発生におけるスフィンゴ糖脂質の役割 (2012)
  • Author(s): 千葉 雄太、中村 卓史、成瀬 正啓、池内 友子、新垣 真紀子、福本 敏
  • Organizer: 第54回歯科基礎医学会学術大会総会
  • Place of Presentation: 郡山
• [Presentation] エピプロフィンノックアウトマウスモデルの解析 (2012)
  • Author(s): 中村 卓史
  • Organizer: 第54回歯科基礎医学会学術大会総会
  • Place of Presentation: 郡山(招待講演)
• [Book] 内分泌糖尿病代謝内科ー新規転写因子エピプロフィンによる副甲状腺ホルモン発現制御 (2014)
  • Author(s): 中村 卓史，福本 敏，中村 はな，千葉 雄太，山田 吉彦，岩本 容泰
  • Total Pages: 206
  • Publisher: 科学論評社