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Regulation of cartilage degeneration and innervation by DUSP-1 in the development of osteoarthritis

Research Project

Project/Area Number 16K10840
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionTokyo Medical University

Principal Investigator

Sawaji Yasunobu  東京医科大学, 医学部, 助教(特任) (20571152)

Co-Investigator(Kenkyū-buntansha) 山本 謙吾  東京医科大学, 医学部, 主任教授 (10246316)
宍戸 孝明  東京医科大学, 医学部, 准教授 (70266500)
正岡 利紀  東京医科大学, 医学部, 准教授 (70256270)
遠藤 健司  東京医科大学, 医学部, 准教授 (90266479)
立岩 俊之  東京医科大学, 医学部, 講師 (00424630)
Research Collaborator MAEKAWA Asato  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords変形性関節症 / 軟骨変性 / 神経侵入 / DUSP-1 / 神経成長因子 / 細胞外基質分解酵素 / 細胞内情報伝達
Outline of Final Research Achievements

Disease modifying drugs for osteoarthritis (OA) have yet to be established. This study investigated the involvement of inflammatory signaling pathway by focusing on MAP kinases and their endogenous phosphatase, DUSP1 in the development of OA. Expression of nerve growth factor (associated with innervation) and matrix metalloproteinases (associated with cartilage degeneration) induced by IL-1 was enhanced in DUSP1 knocked down human synovial fibroblasts. This study sheds light on DUSP1 as a novel target molecule for the conservative treatment of OA.

Academic Significance and Societal Importance of the Research Achievements

近年,細胞内情報伝達分子を標的とした薬剤開発が様々な疾患に適用されている.本研究ではMAP kinaseの3種類のサブタイプ(ERK, p38およびJNK)の阻害剤単独では,OA病態形成の制御は困難であること見出し,これらを包括的に制御しうるDUSP1にその可能性を見出した点は学術的意義のある研究といえる.また,超高齢化社会において患者数の増加が不可避なOAに対する根本的保存療法が確立されていない現状において,DUSP1を調節することでOA病態制御の可能性を見出したことは,今後の新規OA治療薬開発への礎となることが強く期待され,社会的意義の高い研究であると思われる.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (7 results)

All 2018 2016

All Journal Article (2 results) (of which Peer Reviewed: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Limited efficacy of COX-2 inhibitors on nerve growth factor and metalloproteinases expressions in human synovial fibroblasts2016

    • Author(s)
      Makiko Yorifuji, Yasunobu Sawaji, Kenji Endo, Taiichi Kosaka, Kengo Yamamoto
    • Journal Title

      Journal of Orthopaedic Science

      Volume: 21 Issue: 3 Pages: 381-388

    • DOI

      10.1016/j.jos.2016.01.004

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] 変形性関節症に対する薬物治療の展望2016

    • Author(s)
      澤地恭昇,宮本泰典,依藤麻紀子,正岡利紀,宍戸孝明,山本謙吾
    • Journal Title

      整形・災害外科

      Volume: 59 Pages: 1181-1188

    • Related Report
      2016 Research-status Report
  • [Presentation] DUSP-1によるヒト変形性関節症の軟骨変性および神経侵入制御の解明2018

    • Author(s)
      前川麻人,澤地恭昇,遠藤健司,日下部拓哉,小西隆允,正岡利紀,宍戸孝明,山本 謙吾
    • Organizer
      第11回日本運動器疼痛学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] DUSP-1によるヒト変形性関節症の軟骨変性および神経侵入制御の解明2018

    • Author(s)
      前川麻人,澤地恭昇,遠藤健司, 日下部拓哉,小西隆允,立岩俊之,正岡利紀,山本謙吾
    • Organizer
      第33回日本整形外科学会基礎学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒト関節滑膜細胞におけるPGE2によるNGFおよびMMP発現抑制へのDUSP1の関与2018

    • Author(s)
      前川麻人,澤地恭昇,遠藤健司, 日下部拓哉,小西隆允,正岡利紀,宍戸孝明,山本謙吾
    • Organizer
      第16回整形外科痛みを語る会
    • Related Report
      2018 Annual Research Report
  • [Presentation] DUSP-1 Involves In The Mechanism Of PGE2 Suppression Of MMPs And NGF In Human Synovial Cells2018

    • Author(s)
      Asato Maekawa, Yasunobu Sawaji, Kenji Endo, Takuya Kusakabe, Takamitu Konishi, Toshiyuki Tateiwa, Toshinori Masaoka, Takaaki Shishido, Kengo Yamamoto
    • Organizer
      The 28th Japanese-Korean Combined Orthopaedic Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 変形性関節症の病態形成過程における選択的COX-2阻害剤の有用性の相違2016

    • Author(s)
      澤地恭昇,依藤麻紀子,宮本泰典,立岩俊之,正岡利紀,宍戸孝明,山本謙吾
    • Organizer
      第31回 日本整形外科学会基礎学術集会
    • Place of Presentation
      福岡国際会議場 (福岡県福岡市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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