• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Molecular mechanisms underlying homeostasis of artiuclar joint

Research Project

Project/Area Number 20H03799
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionThe University of Tokyo

Principal Investigator

Saito Taku  東京大学, 医学部附属病院, 准教授 (30456107)

Co-Investigator(Kenkyū-buntansha) 山神 良太  東京大学, 医学部附属病院, 助教 (00722191)
森 大典  東京大学, 医学部附属病院, 届出研究員 (60835354)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2022: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2021: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2020: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Keywords関節恒常性 / 関節運動 / 滑膜 / 軟骨 / 変形性関節症 / 廃用症候群 / 整形外科学
Outline of Research at the Start

本研究では、滑膜のメカノバイオロジーという新たな視点から、関節維持機構の真相に迫る。マウスをベースに、ヒトの組織や細胞を含んだ多様な解析手法とシングルセル解析、微小発現解析などの最新の分子生物学的手法を融合させ、通常状態の滑膜から、恒常性が破綻した滑膜まで、さまざまな状態における滑膜およびその変化を理解し、滑膜が関節全体でどのように維持機構として働いているかを解析し、関節の恒常性維持・制御メカニズムの全貌解明を目指す。

Outline of Final Research Achievements

We established a minimized mechanical stress (MMS) model by knee joint immobilization of mice that were suspended by their tails. Histological examination showed synovitis followed by cartilage degeneration. Joint motion could cancel the alteration. Bulk RNA-seq of MMS model mice showed remarkable increases in expression of catabolic factors in synovium and remarkable decreases of matrix proteins in cartilage. On the basis of the cartilage gene expression alterations, Ingenuity Pathway Analysis estimated dozens of upstream cytokines and growth factors, including Spp1 and Il-1β, whose expressions were increased in the MMS model synovium. ScRNA-seq of synovium detected specific subsets among activated fibroblasts and activated macrophages, which expressed cytokines and growth factors responsible for cartilage degeneration. Moreover, ligand-receptor analysis indicated dynamic interactions between the two MMS-specific subsets through these secreted molecules.

Academic Significance and Societal Importance of the Research Achievements

関節を動かすことは関節の機能維持に重要であり、長期間関節を固定すると関節は拘縮し、軟骨は変性するが、そのメカニズムは未だ解明されていない。本研究では、廃用関節で関節変性が起きるメカニズムの一端を初めて明らかにしたという点に意義がある。関節運動は滑膜を介した恒常性維持に不可欠であり、さらに軟骨を含めた関節全体の恒常性維持にも貢献することが示され、今後進みゆく高齢化社会での廃用関節の治療への応用が期待される。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • Research Products

    (15 results)

All 2022 2021 Other

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (8 results) (of which Invited: 5 results) Remarks (1 results)

  • [Journal Article] Inflammatory Arthritis and Bone Metabolism Regulated by Type 2 Innate and Adaptive Immunity2022

    • Author(s)
      Omata Yasunori、Frech Michael、Saito Taku、Schett Georg、Zaiss Mario M.、Tanaka Sakae
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 3 Pages: 1104-1104

    • DOI

      10.3390/ijms23031104

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Automatic Detection of Medial and Lateral Compartments from Histological Sections of Mouse Knee Joints Using the Single-Shot Multibox Detector Algorithm2022

    • Author(s)
      Mori Yoshifumi、Oichi Takeshi、Enomoto-Iwamoto Motomi、Saito Taku
    • Journal Title

      CARTILAGE

      Volume: 13 Issue: 1

    • DOI

      10.1177/19476035221074009

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The superficial zone of articular cartilage2022

    • Author(s)
      Saito Taku
    • Journal Title

      Inflammation and Regeneration

      Volume: 42 Issue: 1

    • DOI

      10.1186/s41232-022-00202-0

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Regulation of osteoarthritis development by ADAM17/Tace in articular cartilage2021

    • Author(s)
      Kaneko Taizo、Horiuchi Keisuke、Chijimatsu Ryota、Mori Daisuke、Nagata Kosei、Omata Yasunori、Yano Fumiko、Inui Hiroshi、Moro Toru、Tanaka Sakae、Saito Taku
    • Journal Title

      Journal of Bone and Mineral Metabolism

      Volume: 40 Issue: 2 Pages: 196-207

    • DOI

      10.1007/s00774-021-01278-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Divergence in chondrogenic potential between in vitro and in vivo of adipose- and synovial-stem cells from mouse and human2021

    • Author(s)
      Chijimatsu Ryota、Miwa Satoshi、Okamura Gensuke、Miyahara Junya、Tachibana Naohiro、Ishikura Hisatoshi、Higuchi Junya、Maenohara Yuji、Tsuji Shinsaku、Sameshima Shin、Takagi Kentaro、Nakazato Keiu、Kawaguchi Kohei、Yamagami Ryota、Inui Hiroshi、Taketomi Shuji、Tanaka Sakae、Saito Taku
    • Journal Title

      Stem Cell Research & Therapy

      Volume: 12 Issue: 1

    • DOI

      10.1186/s13287-021-02485-5

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TRPV2 is involved in induction of lubricin and suppression of ectopic endochondral ossification in articular joints2021

    • Author(s)
      Nakamoto Hideki、Katanosaka Yuki、Chijimatsu Ryota、Mori Daisuke、Xuan Fengjun、Yano Fumiko、Omata Yasunori、Maenohara Yuji、Murahashi Yasutaka、Kawaguchi Kohei、Yamagami Ryota、Inui Hiroshi、Taketomi Shuji、Taniguchi Yuki、Kanagawa Motoi、Naruse Keiji、Tanaka Sakae、Saito Taku
    • Journal Title

      Arthritis & Rheumatology

      Volume: - Issue: 8 Pages: 1441-1450

    • DOI

      10.1002/art.41684

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 廃用関節では滑膜マクロファージおよび滑膜線維芽細胞の特異的クラスターが軟骨変性に寄与する2022

    • Author(s)
      石倉 久年、齋藤 琢、他
    • Organizer
      第34回軟骨代謝学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 廃用関節では滑膜マクロファージおよび滑膜線維芽細胞の特異的クラスターが軟骨変性に寄与する2022

    • Author(s)
      石倉 久年、齋藤 琢、他
    • Organizer
      第61回日本生体医工学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 廃用関節では滑膜マクロファージおよび滑膜線維芽細胞の特異的クラスターが軟骨変性に寄与する2022

    • Author(s)
      石倉 久年、齋藤 琢、他
    • Organizer
      第8回日本筋学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 変形性関節症の分子機序2021

    • Author(s)
      齋藤琢
    • Organizer
      第49回日本関節病学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 変形性関節症の分子病態からみたPRP/APSと幹細胞治療2021

    • Author(s)
      齋藤琢
    • Organizer
      第36回日本整形外科学会基礎学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 関節軟骨の維持機構2021

    • Author(s)
      齋藤琢
    • Organizer
      第42回日本炎症・再生医学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 脂肪由来幹細胞を用いた変形性関節症治療2021

    • Author(s)
      齋藤琢
    • Organizer
      第94回日本整形外科学会学術総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 変形性関節症における骨・軟骨連関2021

    • Author(s)
      齋藤琢
    • Organizer
      第94回日本整形外科学会学術総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Remarks] 東京大学医学部附属病院 整形外科・脊椎外科

    • URL

      http://www.u-tokyo-ortho.jp/

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi