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The mechanisms of arthritic diseases-specific cartilage destruction by MMP molecules

Research Project

Project/Area Number 25462379
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Araki Yasuto  埼玉医科大学, 医学部, 講師 (10580839)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords関節リウマチ / 変形性関節症 / MMP / エピジェネティクス / ヒストン修飾 / IL-6 / MMP分子 / 関節炎 / エピゲノム
Outline of Final Research Achievements

To clarify dysfunctions of epigenetic regulation in the pathogenesis of rheumatiod arthritis (RA), gene expression of matrix metalloproteinases (MMPs), which are matrix-degrading enzymes, and histone modifications in the promoters were examined in RA synovial fibroblasts (SFs) and osteoarthritis (OA) SFs. Gene expression of MMP-1, 3, 9, and 13 was significantly higher in RASFs than in OASFs. Histone methylation profiles in the MMP promoters were consistent with the MMP gene expression. In addition, MMP-1, 3, and 13 genes were responsive to IL-6 stimulation in RASFs. Taken together, it is suggested that histone methylation plays an important role in the activation of RASFs.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (15 results)

All 2016 2015 2014 2013 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (9 results) (of which Int'l Joint Research: 1 results) Remarks (2 results)

  • [Journal Article] Histone Methylation and STAT-3 Differentially Regulate Interleukin-6-Induced Matrix Metalloproteinase Gene Activation in Rheumatoid Arthritis Synovial Fibroblasts.2016

    • Author(s)
      Araki Y, Tsuzuki Wada T, Aizaki Y, Sato K, Yokota K, Fujimoto K, Kim YT, Oda H, Kurokawa R, Mimura
    • Journal Title

      Arthritis Rheumatol.

      Volume: 68 Issue: 5 Pages: 1111-23

    • DOI

      10.1002/art.39563

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aberrant histone acetylation contributes to elevated interleukin-6 production in rheumatoid arthritis synovial fibroblasts2014

    • Author(s)
      Wada TT, Araki Y, Sato K, Aizaki Y, Yokota K, Kim YT, Oda H, Kurokawa R, Mimura T.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 444 Issue: 4 Pages: 682-686

    • DOI

      10.1016/j.bbrc.2014.01.195

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Combination of tumor necrosis factor α and interleukin-6 induces mouse osteoclast-like cells with bone resorption activity both in vitro and in vivo2014

    • Author(s)
      Yokota K, Sato K, Miyazaki T, Kitaura H, Kayama H, Miyoshi F, Araki Y, Akiyama Y, Takeda K, Mimura T.
    • Journal Title

      Arthritis Rheumatol.

      Volume: 66 Issue: 1 Pages: 121-129

    • DOI

      10.1002/art.38218

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Implicated role of liposarcoma related fusion oncoprotein TLS-CHOP in the dysregulaiton of arginine-specific methylation through PRMT12013

    • Author(s)
      Kenta Fujimoto, Shigeki Arai, Maki Matsubara, Kun Du, Yasuto Araki, Akio Matsushita, Riki Kurokawa
    • Journal Title

      Cell Biology

      Volume: Vol.1、No.2 Issue: 2 Pages: 18-23

    • DOI

      10.11648/j.cb.20130102.11

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Altered profiles of histone lysine methylation affect MMP gene transcription in rheumatoid arthritis synovial fibroblasts2016

    • Author(s)
      Araki Y, Wada TT, Aizaki Y, Kajiyama H, Yokota K, Sato K, Asanuma YF, Kim YT, Oda H, Mimura T
    • Organizer
      Annual European Congress of Rheumatology EULAR 2016
    • Place of Presentation
      ExCel London, UK
    • Year and Date
      2016-06-10
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The epigenetic mechanism of constitutive and IL-6-induced MMP gene activation in rheumatoid arthritis synovial fibroblasts2016

    • Author(s)
      Yasuto Araki, Takuma Tsuzuki Wada, Yoshimi Aizaki, Hiroshi Kajiyama, Kazuhiro Yokota, Kojiro Sato, Yu Funakubo Asanuma, Yoon-Taek Kim, Hiromi Oda, Toshihide Mimura
    • Organizer
      第60回日本リウマチ学会総会・学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-04-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] 関節リウマチ滑膜線維芽細胞におけるH3K4ヒストンメチル基転移酵素によるケモカイン遺伝子発現の制御2015

    • Author(s)
      荒木靖人、和田琢、相崎良美、佐藤浩二郎、黒川 理樹、三村俊英
    • Organizer
      第9回日本エピジェネティクス研究会年会
    • Place of Presentation
      東京一ツ橋学術総合センター(東京都千代田区)
    • Year and Date
      2015-05-25
    • Related Report
      2015 Annual Research Report
  • [Presentation] 関節リウマチ滑膜線維芽細胞におけるヒストン3リシン4メチル基転移酵素の異常2015

    • Author(s)
      荒木靖人、和田琢、相崎良美、横田和浩、梶山浩、秋葉春彦、佐藤浩二郎、秋山雄次、金潤澤、織田弘美、三村俊英
    • Organizer
      第59回日本リウマチ学会総会・学術集会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-04-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] 関節リウマチ滑膜線維芽細胞のIL-6依存性MMP遺伝子転写活性化におけるヒストンメチル化の役割

    • Author(s)
      荒木靖人、和田琢、藤本健太、黒川理樹、三村俊英
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートピアアイランド
    • Related Report
      2013 Research-status Report
  • [Presentation] 関節リウマチ滑膜線維芽細胞におけるヒストンメチル化によるIL-6誘導性MMP遺伝子転写活性化の制御機構

    • Author(s)
      荒木靖人、和田琢、黒澤奈津子、相崎良美、藤本健太、佐藤浩二郎、横田和浩、三由文彦、金潤澤、織田弘美、黒川理樹、三村俊英
    • Organizer
      第11回RCGMフロンティアシンポジウム
    • Place of Presentation
      埼玉医科大学日高キャンパス 創立30周年記念講堂
    • Related Report
      2013 Research-status Report
  • [Presentation] Altered histone methylation is associated with IL-6 dependent matrix metalloproteinases gene transcriptional activation in rheumatoid arthritis synovial fibroblasts

    • Author(s)
      Araki Y, Wada TT, Sato K, Yokota K, Miyoshi F, Asanuma YF, Akiyama Y, Mimura T
    • Organizer
      American College of Rheumatology, the Annual Scientific Meeting 2013
    • Place of Presentation
      San Diego Convention Center, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] 関節リウマチ滑膜線維芽細胞のIL-6依存性MMP遺伝子転写活性化におけるヒストンメチル化の役割

    • Author(s)
      荒木靖人、和田琢、佐藤浩二郎、織田弘美、黒川 理樹、三村俊英
    • Organizer
      第7回日本エピジェネティクス研究会年会
    • Place of Presentation
      奈良新公会堂
    • Related Report
      2013 Research-status Report
  • [Presentation] 関節リウマチ滑膜線維芽細胞のIL-6依存性MMP遺伝子転写活性化におけるヒストンメチル化の役割

    • Author(s)
      荒木靖人、和田琢、佐藤浩二郎、横田和浩、三由 文彦、梶山浩、舟久保ゆう、金潤澤、織田弘美、秋 山雄次、三村俊英
    • Organizer
      第57回日本リウマチ学会総会・学術集会
    • Place of Presentation
      京都国際会議場
    • Related Report
      2013 Research-status Report
  • [Remarks] 関節リウマチ滑膜線維芽細胞におけるエピジェネティクス異常の解明

    • URL

      http://www.saitama-med.ac.jp/uinfo/riumachi/Dr.Araki.html

    • Related Report
      2015 Annual Research Report
  • [Remarks] 埼玉医科大学リウマチ膠原病科・研究内容

    • URL

      http://www.saitama-med.ac.jp/uinfo/riumachi/Dr.Araki.html

    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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