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Drug development for osteoarthritis(OA) by drug screening for transcriptional activation of SOX9

Research Project

Project/Area Number 22659270
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Orthopaedic surgery
Research InstitutionNagoya University

Principal Investigator

KANEKO Hiroshi  名古屋大学, 大学院・医学系研究科, 寄附講座助教 (60566975)

Co-Investigator(Kenkyū-buntansha) KITOH Hiroshi  名古屋大学, 医学部附属病院, 講師 (40291174)
Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,350,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2010: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsSOX9遺伝子 / 薬効スクリーニング / 軟骨細胞 / 軟骨再生 / オフラベル治療薬 / プロモーター / ルシフェラーゼ / 細胞培養 / SOX9
Research Abstract

A transcription factor SOX9 is a key regulator of cartilage metabolism. Overexpression of SOX9 gene in osteoarthritis(OA) articular cartilage stimulates extracellular matrix synthesis and the expression of extracellular matrix components can be restored to levels similar to those in normal. These results suggest that a drug able to enhance SOX9 gene expression is expected to improve symptoms of OA. We screened for off-label effects of 1, 184 chemical compounds approved by FDA to identify a drug able to enhance SOX9 gene expression by activating the promoter region. Finally, two compounds showed beneficial effects.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (25 results)

All 2012 2011 2010

All Journal Article (12 results) (of which Peer Reviewed: 9 results) Presentation (13 results)

  • [Journal Article] Chondro blastoma of the femoral neck as a cause of hip synovitis2012

    • Author(s)
      Kaneko H, Kitoh H, Wasa J, Nishida Y, Ishiguro N.
    • Journal Title

      J Pediatr Orthop

      Volume: 21(2) Pages: 179-182

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chondroblastoma of the femoral neck as a cause of hip synovitis2012

    • Author(s)
      Kaneko H, Kitoh H, Wasa J, Nishida Y, Ishiguro N
    • Journal Title

      J Pediatr Orthop B

      Volume: 21 Issue: 2 Pages: 179-182

    • DOI

      10.1097/bpb.0b013e3283484c31

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel compound heterozygous mutations in the cathepsin K gene in Japanese female siblings with pyknodysostosis2012

    • Author(s)
      Matsushita M, Kitoh H, Kaneko H, Mishima K, Itoh Y, Hattori T, Ishiguro N
    • Journal Title

      Mol Syndromol

      Volume: (in press)(未定) Issue: 6 Pages: 254-258

    • DOI

      10.1159/000336581

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spondy lometaphyseal dysplasia with cone-rod dystrophy2011

    • Author(s)
      Kitoh H, Kaneko H, Kondo M, Yamamoto T, Ishiguro N, Nishimura G.
    • Journal Title

      Am J Med Genet

      Volume: 155A Pages: 845-849

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Early clinical and radiographic characteristics in fibrodysplasia ossificans progressiva : A report of two cases2011

    • Author(s)
      Mishima K, Kitoh H, Katagiri T, Kaneko H, Ishiguro N.
    • Journal Title

      J Bone Joint Surg

      Volume: 93-A

    • Related Report
      2011 Final Research Report
  • [Journal Article] Hyperuricemia cosegregating with osteogenesis imperfecta isassociated with a mutation in GPATCH82011

    • Author(s)
      Kaneko H, Kitoh H, Matsuura T, Masuda A, Ito M, Mottes M, Rauch F, Ishiguro N, Ohno K.
    • Journal Title

      Hum Genet

      Volume: 130(5) Pages: 671-683

    • Related Report
      2011 Final Research Report
  • [Journal Article] Vocabulary SOX92011

    • Author(s)
      金子浩史, 鬼頭浩史, 石黒直樹
    • Journal Title

      臨床雑誌整形外科

      Volume: 62 Pages: 666-666

    • Related Report
      2011 Final Research Report
  • [Journal Article] 股関節炎症状を呈した大腿骨近位部軟骨芽細胞腫の1例2011

    • Author(s)
      金子浩史, 鬼頭浩史, 石黒直樹
    • Journal Title

      日小整誌

      Volume: 20 Pages: 120-124

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ponseti法による先天性内反足の治療成績.全身性疾患や合併奇形の有無による成績の比較.2011

    • Author(s)
      鬼頭浩史, 北小路隆彦, 金子浩史, 馬渕晃好, 三島健一, 石黒直樹
    • Journal Title

      日小整誌

      Volume: 20 Pages: 353-356

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hyperuricemia cosegregating with osteogenesis imperfecta is associated with a mutation in GPATCH82011

    • Author(s)
      Kaneko H, Kitoh H, Matsuura T, Masuda A, Ito M, Mottes M, Rauch F, Ishiguro N, Ohno K
    • Journal Title

      Hum Genet

      Volume: 130 Issue: 5 Pages: 671-683

    • DOI

      10.1007/s00439-011-1006-9

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spondylometaphyseal dysplasia with cone-rod dystrophy2011

    • Author(s)
      Kitoh H, Kaneko H, Kondo M, Yamamoto T, Ishiguro N, Nishimura G
    • Journal Title

      Am J Med Genet A

      Volume: 155A(4) Issue: 4 Pages: 845-9

    • DOI

      10.1002/ajmg.a.33898

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Early clinical and radiographic characteristics in fibrodysplasia ossificans progressiva : a report of two cases2011

    • Author(s)
      Mishima K, Kitoh H, Katagiri T, Kaneko H, Ishiguro N
    • Journal Title

      J Bone Joint Surg Am

      Volume: 93(10) Issue: 10 Pages: e52(1)-e52(5)

    • DOI

      10.2106/jbjs.j.01443

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] 遺伝子に変異を認めたsmall patella syndromeの非定型例2011

    • Author(s)
      金子浩史,鬼頭浩史,馬渕晃好,三島健一,松下雅樹,石黒直樹,西村玄
    • Organizer
      第23回日本整形外科学会骨系統疾患研究会
    • Place of Presentation
      京都
    • Year and Date
      2011-12-09
    • Related Report
      2011 Final Research Report
  • [Presentation] SOX9遺伝子に変異を認めたsmall patella syndromeの非定型例2011

    • Author(s)
      金子浩史、鬼頭浩史、馬渕晃好、三島健一、松下雅樹、石黒直樹、西村玄
    • Organizer
      第23回日本整形外科学会骨系統疾患研究会
    • Place of Presentation
      京都
    • Year and Date
      2011-12-09
    • Related Report
      2011 Annual Research Report
  • [Presentation] 二分肋骨の5例2011

    • Author(s)
      金子浩史,鬼頭浩史,馬渕晃好,三島健一,石黒直樹
    • Organizer
      第26回東海小児整形外科懇話会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-02-19
    • Related Report
      2011 Final Research Report
  • [Presentation] 重度大腿骨頭すべり症に対する創外固定法による骨切り術2011

    • Author(s)
      鬼頭浩史,金子浩史,馬渕晃好,三島健一,松下雅樹,石黒直樹,北小路隆彦,服部義
    • Organizer
      第22回日本小児整形外科学会
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] 1歳6か月以降に診断された股関節脱臼に対する治療成績2011

    • Author(s)
      金子浩史,鬼頭浩史,馬渕晃好,三島健一,松下雅樹,石黒直樹,岩田浩志,北小路隆彦,服部義
    • Organizer
      第22回日本小児整形外科学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] ペルテス病の治療成績に関連する因子の検討2011

    • Author(s)
      鬼頭浩史,金子浩史,北小路隆彦,服部義,石黒直樹
    • Organizer
      第50回小児股関節研究会
    • Place of Presentation
      諏訪
    • Related Report
      2011 Final Research Report
  • [Presentation] 進行性骨化性線維異形成症における早期(骨化発症前)の臨床的, X線学的特徴2011

    • Author(s)
      鬼頭浩史,三島健一,金子浩史,石黒直樹
    • Organizer
      第84回日本整形外科学会
    • Place of Presentation
      横浜
    • Related Report
      2011 Final Research Report
  • [Presentation] Drug screening for transcriptional activation of SOX92011

    • Author(s)
      Kaneko H, Kitoh H, Yamamoto R, IshiguroN, Ohno K
    • Organizer
      57th ORS Annual Meeting
    • Place of Presentation
      Long Beach, CA,米国
    • Related Report
      2011 Final Research Report
  • [Presentation] Drug screening for transcriptional activation of SOX92011

    • Author(s)
      金子浩史
    • Organizer
      2011 Annual Meeting of the Orthopaedic Research Society
    • Place of Presentation
      ロングビーチコンベンションセンター(California, USA)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 著明な肩甲骨低形成を伴うsmall patella syndromeの1例2010

    • Author(s)
      金子浩史,鬼頭浩史,馬渕晃好,三島健一,石黒直樹,西村玄
    • Organizer
      第22回日本整形外科学会骨系統疾患研究会
    • Place of Presentation
      徳島
    • Year and Date
      2010-11-27
    • Related Report
      2011 Final Research Report
  • [Presentation] Ponseti法による先天性内反足の治療成績.全身性疾患や合併奇形の有無による成績の比較2010

    • Author(s)
      鬼頭浩史,金子浩史,北小路隆彦,石黒直樹
    • Organizer
      第21回整形外科学会
    • Place of Presentation
      徳島
    • Related Report
      2011 Final Research Report
  • [Presentation] 非典型的大腿骨頭すべり症の特徴2010

    • Author(s)
      金子浩史,鬼頭浩史,馬渕晃好,三島健一,石黒直樹
    • Organizer
      第21回日本小児整形外科学会学術集会
    • Place of Presentation
      徳島
    • Related Report
      2011 Final Research Report
  • [Presentation] 骨系統疾患に対する培養骨髄細胞移植を併用した骨延長術2010

    • Author(s)
      鬼頭浩史、金子浩史、石黒直樹
    • Organizer
      第83回日本整形外科学会
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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