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Analysis of roles of HIF-2a in odontoblast differentiation for regeneration of tooth germs using iPS cells.

Research Project

Project/Area Number 19K24085
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0907:Oral science and related fields
Research InstitutionTohoku University

Principal Investigator

KIMURA SEIJI  東北大学, 大学病院, 医員 (40850590)

Project Period (FY) 2019-08-30 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsHIF-2α / 象牙芽細胞 / エナメル芽細胞 / iPS細胞
Outline of Research at the Start

歯性間葉細胞から象牙芽細胞への分化におけるHIF-2αの機能と分子機構を明らかにし、HIF-2αをiPS細胞から歯胚発生能をもつ歯性間葉細胞細胞の樹立に応用することを目的とする。これにより、低酸素応答に着目した歯胚発生制御研究の新展開につながり、また歯の再生に必要なiPS細胞由来の細胞シーズの獲得実現が期待される。

Outline of Final Research Achievements

In the present study, I analyzed the function and molecular mechanism of HIF-2α in tooth germ development to get basic knowledge for applying HIF-2α signaling to generate tooth germs using iPS cells in the future. I have identified a notch signaling molecule as a downstream factor of HIF-2α in tooth germ development, and it has been shown that these factors regulate the differentiation of odontogenic cells.

Academic Significance and Societal Importance of the Research Achievements

これまで歯の発生の分子制御に関する報告が多くなされてきた。しかし、我々が初めて明らかにした、生体において歯胚が低酸素環境にあることを考慮すると、歯原性細胞における低酸素応答による歯胚発生制御の解明が必須である。本研究により世界で初めて、HIFファミリーのうちHIF-2αが歯原性細胞の分化を制御することが示され、さらにその機能はnotchシグナリング因子を介することが明らかとなった。今後、iPS細胞から歯胚発生能をもつ細胞を樹立するうえで、この新規分子メカニズムが重要な役割を担う可能性がある。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (2 results)

All 2021 2020

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results)

  • [Journal Article] Connective tissue growth factor promotes chemotaxis of preosteoblasts through integrin α5 and Ras during tensile force-induced intramembranous osteogenesis2021

    • 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

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Methionine Enkephalin Suppresses Osteocyte Apoptosis Induced by Compressive Force through Regulation of Nuclear Translocation of NFATc12020

    • 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

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access

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Published: 2019-09-03   Modified: 2022-01-27  

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