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2012 Fiscal Year Final Research Report

Analysis of BMP-mediated cartilage formation anddifferentiation, and cartilage repair

Research Project

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Project/Area Number 21390421
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionKyoto University (2011-2012)
Osaka University (2009-2010)

Principal Investigator

TSUMAKI Noriyuki  京都大学, iPS細胞研究所, 教授 (50303938)

Project Period (FY) 2009 – 2012
Keywords軟骨細胞 / 内軟骨性骨化 / ノックアウトマウス / 細胞分化 / HDAC4
Research Abstract

Sox9 in mesenchymal progenitors is important for their differentiation intochondrocytes, but its functions after differentiation into chondrocytes have not beendetermined. To investigate Sox9 function in chondrocytes precisely, we deleted Sox9genes after differentiation into chondrocytes in mice. Sox9 inactivation inchondrocytes resulted in apoptosis. Molecular analysis revealed that Sox9 sustainswhich are involved in chondrocyte differentiation, we discovered that chondrocytehypertrophy was markedly delayed in the growth plate cartilage in mice lacking saltinducible kinase 3 (SIK3). SIK3 was required for anchoring HDAC4 in the cytoplasm,thereby releasing MEF2C, a critical facilitator of chondrocyte hypertrophy, fromsuppression by HDAC4 in the nuclei. From these results, we concluded that SIK3facilitates chondrocyte hypertrophy during formation and maintenance of cartilage

  • Research Products

    (10 results)

All 2012 2011 2009 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (4 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] SIK3 is essential forchondrocyte hypertrophy during skeletaldevelopment in mice2012

    • Author(s)
      Sasagawa,S.,Takemori,H.,Uebi,T.,Ikegami,D.,Hiramatsu,K.,Ikegawa,S.,Yoshikawa,H.and Tsumaki,N.
    • Journal Title

      Development

      Volume: 139巻 Pages: 1153-1163

    • DOI

      DOI10.1242/dev.072652

    • Peer Reviewed
  • [Journal Article] Conditional deletionof Bmpr1ab in differentiatedosteoclasts increases osteoblastic boneformation,increasing volume ofremodeling bone in mice.2011

    • Author(s)
      Okamoto,M.,Murai,J.,Imai,Y.,Ikegami,D.,Kamiya,N.,Kato,S.,Mishita,Y.,Yoshikawa,H.and Tsumaki,N
    • Journal Title

      J.BoneMiner.Res.

      Volume: 26巻 Pages: 2511-22

    • DOI

      DOI:10.1002/jbmr.477

    • Peer Reviewed
  • [Journal Article] Induction ofchondrogenic cells from dermalfibroblast culture by defined factorsdoes not involve a pluripotent state.2011

    • Author(s)
      Outani,H.,Okada,M.,Hiramatsu,K.,Yoshikawa,H and Tsumaki,N.
    • Journal Title

      Biochem.Biophys.Res.Commun.

      Volume: 411巻 Pages: 607-12

    • DOI

      DOI:10.1016/j.bbrc.2011.06.194

    • Peer Reviewed
  • [Journal Article] Essential mesenchymal role of smallGTPase Rac1 in interdigital programmedcell death during limb development.2009

    • Author(s)
      Suzuki D, Yamada A, Amano T, YasuharaR, Kimura A, Sakahara M,Tsumaki N,Takeda S, Tamura M, Nakamura M, Wada N,Nohno T, Shiroishi T, Aiba A, KamijoR.
    • Journal Title

      Dev. Biol.

      Volume: 335 Pages: 396-406

    • Peer Reviewed
  • [Presentation] Directed inductionof chondrogenic cells from mousedermal fibroblast culture2011

    • Author(s)
      Noriyuki Tsumaki
    • Organizer
      1st BioRheumatology International
    • Place of Presentation
      東京
    • Year and Date
      20111114-1116
  • [Presentation] 軟骨細胞リプログラミングと軟骨マトリックス遺伝子発現2011

    • Author(s)
      妻木範行
    • Organizer
      日本整形外科学会基礎学術集会
    • Place of Presentation
      群馬、前橋市
    • Year and Date
      20111020-1021
  • [Presentation] Directed inductionof hyaline chondrogenic cells frommouse adult dermal fibroblast cluturteby defined factors2011

    • Author(s)
      Noriyuki Tsumaki
    • Organizer
      Korean Society OfOsteoporosis
    • Place of Presentation
      Seoul,Korea
    • Year and Date
      20110430-0501
  • [Presentation] Regulatory sequences ofthe a2(XI) collgen chain gene andchondrogenesis2009

    • Author(s)
      妻木範行
    • Organizer
      6th Meeting of BoneBiology Forum
    • Place of Presentation
      静岡市
    • Year and Date
      2009-08-21
  • [Remarks]

    • URL

      http://www.cira.kyoto-u.ac.jp/j/research/tsumaki_summary.html

  • [Patent(Industrial Property Rights)] 軟骨疾患治療薬のスクリーニング方法および軟骨疾患治療用改変軟骨細胞2011

    • Inventor(s)
      妻木範行
    • Industrial Property Rights Holder
      大阪大学医薬基盤研究所
    • Industrial Property Number
      2011-121788
    • Filing Date
      2011-05-31

URL: 

Published: 2014-08-29  

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