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Roles of Bone Morphogenetic Protein 2 in postnatal meniscus homeostasis

Research Project

Project/Area Number 18K09056
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Koga Hideyuki  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30594080)

Co-Investigator(Kenkyū-buntansha) 辻 邦和  東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (20323694)
関矢 一郎  東京医科歯科大学, 統合研究機構, 教授 (10345291)
宗田 大  東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (50190864)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords半月板 / 骨形成因子 / BMP2 / BMP4 / BMP7 / 発生 / 再生 / 損傷後修復 / 円板状半月板 / BMP / 骨形成因子BMP / 恒常性
Outline of Final Research Achievements

To elucidate the physiological roles of Bmp2, Bmp4, and Bmp7 in postnatal joint homeostasis, we have created limb specific Bmp conditional knockout mice (Bmp2c/c;Prx1::cre, Bmp4c/c;Prx1::cre, Bmp7c/c;Prx1::cre) and analyzed age related knee joint phenotypes. We have reported that conditional null mutation of Bmp2 results in the malformation of meniscus and down regulation of type II collagen expression in the superficial region of articular cartilage within 2 weeks after birth. We also reported that conditional null mutation of Bmp7 results in the reduction of proteoglycan contents in articular cartilage after 8 weeks of age. In contrast, we observed subtle morphological changes in articular cartilage and meniscus in the absence of Bmp4 (not published). In this study we focused on the analyses of meniscus formation in the absence of Bmp2 and showed that chondrogenic differentiation of the cells reside in the meniscus primordium was strictly inhibited after birth.

Academic Significance and Societal Importance of the Research Achievements

半月板は関節機能の維持に必須の組織であるにも関わらず、その発生並びに恒常性の分子機序はほとんど解析されていない。近年では、半月板機能の低下が変形性膝関節症の発症並びに増悪に深く関与していることが報告されている。本研究の成果は、半月板機能の維持に必要な分子機序の解明につながることが期待される。

Report

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

    (15 results)

All 2021 2020 2019 2018

All Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Open Access: 5 results) Presentation (5 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Thawed cryopreserved synovial mesenchymal stem cells show comparable effects to cultured cells in the inhibition of osteoarthritis progression in rats.2021

    • Author(s)
      Kiyotaka Horiuchi, Nobutake Ozeki, Kentaro Endo, Mitsuru Mizuno, Hisako Katano, Masako Akiyama, Kunikazu Tsuji, Hideyuki Koga, Ichiro Sekiya
    • Journal Title

      Sci Rep.

      Volume: 11 Issue: 1 Pages: 9683-9683

    • DOI

      10.1038/s41598-021-89239-8

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Arthroscopic Centralization Using Knotless Anchors for Extruded Medial Meniscus.2021

    • Author(s)
      Hideyuki Koga, Tomomasa Nakamura, Yusuke Nakagawa, Nobutake Ozeki, Toshiyuki Ohara, Mikio Shioda, Yuji Kohno, Masaki Amemiya, Ichiro Sekiya.
    • Journal Title

      Arthrosc Tech.

      Volume: 10 Issue: 3 Pages: e639-e645

    • DOI

      10.1016/j.eats.2020.10.051

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synovial mesenchymal stem cells promote the meniscus repair in a novel pig meniscus injury model.2021

    • Author(s)
      1.Ozeki N, Kohno Y, Kushida Y, Watanabe N, Mizuno M, Katano H, Masumoto J, Koga H, Sekiya I.
    • Journal Title

      J Orthop Res

      Volume: 3 Issue: 1 Pages: 177-183

    • DOI

      10.1002/jor.24846

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inhibition of fibrotic changes in infrapatellar fat pad alleviates persistent pain and articular cartilage degeneration in monoiodoacetic acid-induced rat arthritis model2021

    • Author(s)
      An J.-S.、Tsuji K.、Onuma H.、Araya N.、Isono M.、Hoshino T.、Inomata K.、Hino J.、Miyazato M.、Hosoda H.、Kangawa K.、Nakagawa Y.、Katagiri H.、Miyatake K.、Sekiya I.、Muneta T.、Koga H.
    • Journal Title

      Osteoarthritis and Cartilage

      Volume: 29 Issue: 3 Pages: 380-388

    • DOI

      10.1016/j.joca.2020.12.014

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Knee laxity, lateral meniscus tear and distal femur morphology influence pivot shift test grade in ACL injury patients2020

    • Author(s)
      Cui Weiding、Nakagawa Yusuke、Katagiri Hiroki、Otabe Koji、Ohara Toshiyuki、Shioda Mikio、Kohno Yuji、Hoshino Takashi、Yoshihara Aritoshi、Sekiya Ichiro、Koga Hideyuki
    • Journal Title

      Knee Surgery, Sports Traumatology, Arthroscopy

      Volume: 29 Issue: 2 Pages: 633-640

    • DOI

      10.1007/s00167-020-05994-7

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fibrotic changes in the infrapatellar fat pad induce new vessel formation and sensory nerve fiber endings that associate prolonged pain.2020

    • Author(s)
      Onuma H, Tsuji K, Hoshino T, Inomata K, Udo M, Nakagawa Y, Katagiri H, Miyatake K, Watanabe T, Sekiya I, Muneta T, Koga H
    • Journal Title

      J Orthop Res.

      Volume: In press Issue: 6 Pages: 1296-1306

    • DOI

      10.1002/jor.24580

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synovial fluid-derived mesenchymal cells have non-inferior chondrogenic potential and can be utilized for regenerative therapy as substitute for synovium-derived cells.2020

    • Author(s)
      Amemiya M, Tsuji K, Katagiri H, Miyatake K, Nakagawa Y, Sekiya I, Muneta T, Koga H.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 523 Issue: 2 Pages: 465-472

    • DOI

      10.1016/j.bbrc.2019.12.068

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Time course analyses of structural changes in the infrapatellar fat pad and synovial membrane during inflammation-induced persistent pain development in rat knee joint.2019

    • Author(s)
      Inomata K, Tsuji K, Onuma H, Hoshino T, Udo M, Akiyama M, Nakagawa Y, Katagiri H, Miyatake K, Sekiya I, Muneta T, Koga H.
    • Journal Title

      BMC Musculoskelet Disord.

      Volume: 20 Issue: 1 Pages: 8-8

    • DOI

      10.1186/s12891-018-2391-1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Persistent synovial inflammation plays important roles in persistent pain development in the rat knee before cartilage degradation reaches the subchondral bone.2018

    • Author(s)
      Hoshino T, Tsuji K, Onuma H, Udo M, Ueki H, Akiyama M, Abula K, Katagiri H, Miyatake K, Watanabe T, Sekiya I, Koga H, Muneta T.
    • Journal Title

      BMC Musculoskelet Disord.

      Volume: 19 Issue: 1 Pages: 291-291

    • DOI

      10.1186/s12891-018-2221-5

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cartilage/chondrocyte research and osteoarthritis. Emerging drugs for Osteoarthritis.2018

    • Author(s)
      Tsuji K.
    • Journal Title

      Clin Calcium.

      Volume: 28 Pages: 817-824

    • Related Report
      2018 Research-status Report
  • [Presentation] Ramp lesions -Which lesions I fix and how.2021

    • Author(s)
      Hideyuki Koga.
    • Organizer
      19th ESSKA
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アスリートの変形性関節症と競技復帰.2021

    • Author(s)
      古賀 英之
    • Organizer
      第3回 Joint Health Conference
    • Related Report
      2020 Annual Research Report
  • [Presentation] Meniscus -how to preserve?2021

    • Author(s)
      Hideyuki Koga
    • Organizer
      2nd International Knee Day
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Meniscus centralization.2021

    • Author(s)
      Hideyuki Koga
    • Organizer
      2nd International Knee Day
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 半月板機能温存による変形性膝関節症の治療戦略2021

    • Author(s)
      古賀英之
    • Organizer
      第243回 新潟整形外科研究会
    • Related Report
      2020 Annual Research Report

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

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