Elucidation of the functions of IGF1 and Hif1a in tooth development to regulate bioengineered tooth morphogenesis

• Project/Area Number: 18K17241
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57070:Developmental dentistry-related
• Research Institution: Tohoku University
• Principal Investigator: Oyanagi Toshihito 東北大学, 大学病院, 助教 (90805326)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: IGF1 / Hif1α / Hif2α / 歯胚発生 / HIf1a / 歯の発生 / 再生歯形態制御

Outline of Final Research Achievements

In this study, I examined the expression, function, and interaction between IGF1 and Hif1a in tooth morphogenesis, to acquire fundamental knowledge for regulating bioengineered teeth morphology based on IGF1. As a result, it was revealed that IGF1 regulates the morphology of bioengineered teeth by enhancing the proliferation and differentiation of dental epithelial and mesenchymal cells, as well as inducing enamel knot formation. Furthermore, it was suggested that IGFBP, which is closely related to hypoxia signaling, is involved in the differentiation of dental mesenchymal cells into odontoblasts.

Academic Significance and Societal Importance of the Research Achievements

失われた組織や臓器を取り戻すことができる再生医療は、今もなお社会から切望されている。本研究の成果は、IGF1を基軸とした実用的な歯の再生に向けた基盤技術のさらなる発展に寄与するだけでなく、発生過程でIGF1による形態制御を受ける様々な臓器の再生にも応用できる可能性があり、将来の再生医療技術の進歩に役立つ点で非常に大きな意義がある。

Research Products

• [Journal Article] Ten-m/Odz3 regulates migration and differentiation of chondrogenic ATDC5 cells via RhoA-mediated actin reorganization. (2021)
  • Author(s): Takano I, Takeshita N, Yoshida M, Seki D, Oyanagi T, Kimura S, Jiang W, Sasaki K, Sogi C, Kawatsu M, Takano-Yamamoto T.
  • Journal Title: J Cell Physiol. Volume: 236 Issue: 4 Pages: 2906-2919
  • DOI: 10.1002/jcp.30058
  • Peer Reviewed / Open Access
• [Journal Article] Connective tissue growth factor promotes chemotaxis of preosteoblasts through integrin α5 and Ras during tensile force-induced intramembranous osteogenesis (2021)
  • Author(s): Jiang Wei、Takeshita Nobuo、Maeda Toshihiro、Sogi Chisumi、Oyanagi Toshihito、Kimura Seiji、Yoshida Michiko、Sasaki Kiyo、Ito Arata、Takano-Yamamoto Teruko
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 2368-2368
  • DOI: 10.1038/s41598-021-82246-9
  • Peer Reviewed / Open Access
• [Journal Article] Methionine Enkephalin Suppresses Osteocyte Apoptosis Induced by Compressive Force through Regulation of Nuclear Translocation of NFATc1 (2020)
  • Author(s): Sogi Chisumi、Takeshita Nobuo、Jiang Wei、Kim Siyoung、Maeda Toshihiro、Yoshida Michiko、Oyanagi Toshihito、Ito Arata、Kimura Seiji、Seki Daisuke、Takano Ikuko、Sakai Yuichi、Fujiwara Ikuma、Kure Shigeo、Takano‐Yamamoto Teruko
  • Journal Title: JBMR Plus Volume: 4 Issue: 7 Pages: 1-13
  • DOI: 10.1002/jbm4.10369
  • Peer Reviewed / Open Access
• [Journal Article] Insulin-like growth factor 1 modulates bioengineered tooth morphogenesis. (2019)
  • Author(s): Oyanagi T, Takeshita N, Hara M, Ikeda E, Chida T, Seki D, Yoshida M, Seiryu M, Takano I, Kimura S, Oshima M, Tsuji T, Takano-Yamamoto T
  • Journal Title: Sci Rep. Volume: 9 Issue: 1 Pages: 368-368
  • DOI: 10.1038/s41598-018-36863-6
  • NAID: 120006875661
  • Peer Reviewed / Open Access
• [Presentation] MENKは圧縮力による骨細胞のアポトーシスを抑制する (2019)
  • Author(s): 曽木千純、竹下信郎、伊藤新、吉田倫子、大柳俊仁、藤原幾磨、山本照子
  • Organizer: 第37回日本骨代謝学会学術集会
• [Presentation] Odz3はRhoA、アクチン制御を介した遊走促進および分化の促進により、ATDC5の軟骨細胞分化を調整する (2018)
  • Author(s): 高野 郁子、竹下 信郎、関 大輔、大柳 俊仁、吉田 倫子、木村 晴地、川津、 正慶、山本 照子
  • Organizer: 第77回日本矯正歯科学会大会
• [Presentation] IGF1 regulates morphogenesis of bioengineered teeth via proliferation and differentiation of dental epithelial and mesenchymal cells (2018)
  • Author(s): Toshihito Oyanagi, Nobuo Takeshita, Mamiko Hara, Etsuko Ikeda, Toko Chida, Daisuke Seki, Michiko Yoshida, Masahiro Seiryu, Ikuko Takano, Seiji Kimura, Masamitsu Oshima, Takashi Tsuji, Teruko Takano-Yamamoto
  • Organizer: 5th TERMIS World Congress
  • Int'l Joint Research