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Control of extracellular matrix production required for cartilage tissue regeneration

Research Project

Project/Area Number 18K06248
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 44020:Developmental biology-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Shinomura Tamayuki  東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (70206118)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords軟骨 / 再生 / 転写制御 / II型コラーゲン / アグリカン / 転写因子 / エンハンサー / 軟骨細胞 / エピゲノム修飾
Outline of Final Research Achievements

In order to repair the cartilage tissue damaged in disease such as osteoarthritis, it is essential to promote the production of cartilage matrix containing II collagen and aggrecan as the main components. Therefore, in this study, we focused on the type II collagen gene and proceeded to elucidate the control mechanism of its expression. As a result, we found that multiple enhancers are involved in the regulation of this gene expression, and that the function of each enhancer is regulated by epigenetic modification. In addition, we identified ARID5B, KLF4, and SHOX2 as transcription factors that specifically bind to enhancers or promoter. However, further studies are required to fully understand the mechanism that regulate the expression of this gene.

Academic Significance and Societal Importance of the Research Achievements

軟骨基質の発現制御機構を理解することは、軟骨組織の修復再生を制御する上で、非常に重要な課題である。軟骨基質の主要成分であるII型コラーゲンおよびアグリカンの発現制御については、既にSOX9 が深く関わっていることは解っているが、その一方で SOX9 が発現している膵臓等の組織ではII型コラーゲンやアグリカンの発現は全く認められない。したがって、軟骨基質の発現に必要な条件を明らかにすることは、軟骨組織の修復再生に向けた新たな治療法を開発する上で非常に重要な課題である。本研究を通し、II型コラーゲンの発現制御機構について新たな側面が明らかになったことは、学術的にも社会的にも大きな意義を持っている。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (8 results)

All 2021 2019 2018

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Gene expression of type II collagen is regulated by direct interaction with Kruppel-like factor 4 and AT-rich interactive domain 5B2021

    • Author(s)
      Zhang Xiang、Nham Giang Thi Hien、Ito Kazuo、Shinomura Tamayuki
    • Journal Title

      Gene

      Volume: 773 Pages: 145381-145381

    • DOI

      10.1016/j.gene.2020.145381

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of type II collagen and aggrecan genes is regulated through distinct epigenetic modifications of their multiple enhancer elements2019

    • Author(s)
      Nham Giang Thi Hien、Zhang Xiang、Asou Yoshinori、Shinomura Tamayuki
    • Journal Title

      Gene

      Volume: 704 Pages: 134-141

    • DOI

      10.1016/j.gene.2019.04.034

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Suppression of hyaluronan synthesis attenuates the tumorigenicity of low-grade chondrosarcoma2019

    • Author(s)
      Hamada Shunsuke、Nishida Yoshihiro、Zhuo Lisheng、Shinomura Tamayuki、Ikuta Kunihiro、Arai Eisuke、Koike Hiroshi、Kimata Koji、Ushida Takahiro、Ishiguro Naoki
    • Journal Title

      Journal of Orthopaedic Research?

      Volume: 36 Issue: 6 Pages: 1573-1580

    • DOI

      10.1002/jor.23794

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Versican V1 in human endometrial epithelial cells promotes BeWo spheroid adhesion in vitro2019

    • Author(s)
      Miyazaki Yumiko、Horie Akihito、Tani Hirohiko、Ueda Masashi、Okunomiya Asuka、Suginami Koh、Kondoh Eiji、Baba Tsukasa、Konishi Ikuo、Shinomura Tamayuki、Sato Yukiyasu
    • Journal Title

      Reproduction

      Volume: 157 Pages: 53-64

    • DOI

      10.1530/rep-18-0333

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Expression of type II collagen and aggrecan genes is regulated through distinct epigenetic modifications of their multiple enhancer elements2019

    • Author(s)
      Giant Thi Hien Nham, Xiang Zhang, Tamayuki Shinomura
    • Organizer
      日本生化学会
    • Related Report
      2019 Research-status Report
  • [Presentation] II型コラーゲンの遺伝子発現を制御するエンハンサー特異的転写因子の同定2019

    • Author(s)
      張 響、ジャン ニャン、篠村 多摩之
    • Organizer
      日本軟骨代謝学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Expression of type II collagen and aggrecan genes is regulated through the distinct epigenetic modification of multiple enhancer elements2019

    • Author(s)
      Tamayuki Shinomura
    • Organizer
      Gordon Research Conference on Cartilage Biology and Pathology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Identification of an enhancer-specific transcription factor regulating type II collagen gene expression2018

    • Author(s)
      Zhang Xiang, Nham T.H. Giant, Tamayuki Shinomura
    • Organizer
      The 6th Tri-University Consortium on Oral Science and Education
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-01-27  

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