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Integrative Study of transcriptional network systems during enchondral ossification

Research Project

Project/Area Number 20229010
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field Functional basic dentistry
Research InstitutionOsaka University

Principal Investigator

YONEDA Toshiyuki  Osaka University, 大学院・歯学研究科, 教授 (80142313)

Co-Investigator(Renkei-kenkyūsha) NISHIMURA Riko  大阪大学, 大学院・歯学研究科, 准教授 (60294112)
HATA Kenji  大阪大学, 大学院・歯学研究科, 講師 (80444496)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥213,330,000 (Direct Cost: ¥164,100,000、Indirect Cost: ¥49,230,000)
Fiscal Year 2010: ¥72,800,000 (Direct Cost: ¥56,000,000、Indirect Cost: ¥16,800,000)
Fiscal Year 2009: ¥72,800,000 (Direct Cost: ¥56,000,000、Indirect Cost: ¥16,800,000)
Fiscal Year 2008: ¥67,730,000 (Direct Cost: ¥52,100,000、Indirect Cost: ¥15,630,000)
KeywordsSox9 / 軟骨分化 / 転写制御 / Runx2
Research Abstract

Enchondral ossification is very unique and complex biological event which is harmoniously and strictly regulated by several growth factors and cytokines. These factors regulate enchondral ossification by controlling intracellular signaling and transcription factors. Transcription factors, Sox9 and Runx2, play essential roles in enchondral ossification. We found that p54^<nrb> couples transcription to mRNA maturation during enchondral ossification by forming transcriptional complex with Sox9. In contrast, Arid5a and Znf219, both of which form transcriptional complex with Sox9, play a role in chondrocyte differentiation in association with Sox9. In addition, we found that Sox9 forms negative-feedback loop with Ihh/Gli signaling for late stage of chondrogenesis by up-regulating PTHrP expression. Furthermore, we identified that a transcription factor, Dmrt2, links Sox9 function to Runx2. Collectively, our findings provide novel insights into molecular basis of enchondral ossification.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (45 results)

All 2011 2010 2009 2008

All Journal Article (24 results) (of which Peer Reviewed: 22 results) Presentation (18 results) Book (3 results)

  • [Journal Article] Distinct mechanisms are responsible for osteopenia and growth retardation in OASIS-deficient mice.2011

    • Author(s)
      Murakami T, Hino S, Nishimura R, Yoneda T, Wanaka A, Imaizumi K
    • Journal Title

      Bone 48

      Pages: 514-523

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Arid5a cooperates with Sox9 to stimulate chondrocyte-specific transcription.2011

    • Author(s)
      Amano K, Hata K, Muramatsu S, Wakabayashi M, Takigawa Y, Ono K, Nakanishi M, Takashima R, Kogo M, Matsuda A, Nishimura R, Yoneda T
    • Journal Title

      Mol Biol Cell 22

      Pages: 1300-1311

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cellular ATP synthesis mediated by type III sodium-dependent phosphate transporter Pit-1 is critical to chondrogenesis.2011

    • Author(s)
      Sugita A, Kawai S, Hayashibara T, Amano A, Ooshima T, Michigami T, Yoshikawa H, Yoneda T.
    • Journal Title

      J Biol Chem 286

      Pages: 3094-3103

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cellular ATP synthesis mediated by type III sodium-dependent phosphate transporter Pit-1 is critical to chondrogenesis.2011

    • Author(s)
      Sugita A, Yoneda T, et al.
    • Journal Title

      Journal Biological Chemistry

      Volume: Vol 286 Pages: 3094-3103

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Arid5a cooperates with Sox9 to stimulate chondrocyte-specific transcription.2011

    • Author(s)
      Amano K, Yoneda T
    • Journal Title

      Molecular Biology of the Cell

      Volume: (印刷中)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A transcription factor Znf219 regulates chondrocyte differentiation by assembling transcription factory with Sox9.2010

    • Author(s)
      Takigawa Y, Hata K, Muramatsu S, Amano K, Ono K, Wakabayashi M, Matsuda A, Takada K, Nishimura R, Yoneda T.
    • Journal Title

      J Cell Sci 123

      Pages: 3780-3788

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] オステオポンチン、オステオネクチン2010

    • Author(s)
      西村理行
    • Journal Title

      血液・尿化学検査 日本臨牀増刊号

      Pages: 233-235

    • Related Report
      2010 Final Research Report
  • [Journal Article] A transcription factor Znf219 regulates chondrocyte differentiation by assembling transcription factory with Sox9.2010

    • Author(s)
      Takigawa Y, Yoneda T, et al.
    • Journal Title

      J Cell Science

      Volume: Vol 123 Pages: 3780-3788

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of ER stress response by BBF2H7/Sec23a pathway is essential for chondrogenesis.2009

    • Author(s)
      Saito A, Hino S, Murakami T, Kondo S, Kanemoto S, Sekiya H, Saitoh M, Nishimura R, Yoneda T, Furuichi T, Ikegawa S,Ikawa M, Okabe M, ImaizumiK
    • Journal Title

      Nature Cell Biol 11

      Pages: 1197-1204

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The signaling mediated by the ER stress transducer. OASIS is involved in bone formation.2009

    • Author(s)
      Murakami T, Saito A, Hino S, Kondo S, Kanemoto S, Chihara K, Sekiya H, Tsumagari K, Ochiai K, Yoshinaga K,Saitoh M, Nishimura R, Yoneda T, Kou I, Furuichi T, Ikegawa I, Ikawa M, Okabe M, Wanaka A, Imaizumi K
    • Journal Title

      Nature Cell Biol 11

      Pages: 1205-1211

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A Novel Role for TGF-β1 in Bone Remodeling.2009

    • Author(s)
      西村理行
    • Journal Title

      IBMS BoneKey 6

      Pages: 434-438

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sox9 family members negatively regulate maturation and calcification of chondrocytes through up-regulation of PTHrP.2009

    • Author(s)
      Amano K, Hata K, Suigita A, Takigawa Y, Ono K, Wakabayashi M, Kogo M, Nishimura R, Yoneda T
    • Journal Title

      Mol Biol Cell 20

      Pages: 4541-4551

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of ER stress response by BBF2H7/Sec23a pathway is essential for chondrogenesis.2009

    • Author(s)
      Saito, et al.
    • Journal Title

      Nature Cell Biol 11

      Pages: 1197-1204

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The signaling mediated by the ER stress transducer. OASIS is involved in bone formation.2009

    • Author(s)
      Murakami, et al.
    • Journal Title

      Nature Cell Biol 11

      Pages: 1205-1211

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sox9 family members negatively regulate maturation and calcification of chondrocytes through up-regulation of PTHrP.2009

    • Author(s)
      Amano, et al.
    • Journal Title

      mol Biol Cell 20

      Pages: 4541-4551

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Signal transduction and transcriptional regulation during mesenchymal cell differentiation.2008

    • Author(s)
      Nishimura R, Hata K, Ikeda F, Ichida F, Shimoyama A, Matsubara T, Wada W, Amano K, Yoneda T.
    • Journal Title

      J Bone Miner Metab 26

      Pages: 203-121

    • NAID

      10024457887

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Paraspeckle protein p54nrb links Sox9-mediated transcription with RNA processing during chondrogenesis in mice.2008

    • Author(s)
      Hata K, Nishimura R, Muramatsu S, Matsuda A, Matsubara T, Amano K, Ikeda F, Harley VR, YonedaT
    • Journal Title

      J Clin Invest 118

      Pages: 3098-3108

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Msx2 stimulates chondrocyte maturation by controlling Ihh expression.2008

    • Author(s)
      Amano K, Ichida F, Sugita A, Hata K, Wada M, Takigawa Y, Nakanishi M, Kogo M, Nishimura R, Yoneda Y
    • Journal Title

      J Biol Chem 283

      Pages: 29513-29521

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 内軟骨性骨形成の分子制御機構2008

    • Author(s)
      西村理行、波多賢二、天野克比古、滝川陽子、小野孝一郎、米田俊之
    • Journal Title

      最新医学 63

      Pages: 2170-2175

    • Related Report
      2010 Final Research Report
  • [Journal Article] BMP2 regulates Osterix through Msx2 and Runx2 during osteoblast differentiation.2008

    • Author(s)
      Matsubara T, Kida K, Yamaguchi A, Hata K, Ichida F, Meguro H, Aruratani H, Nishimura R, Yoneda T
    • Journal Title

      J Biol Chem 283

      Pages: 29119-29125

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] PIAS3 negatively regulates RANKL-mediated osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblasts.2008

    • Author(s)
      Hikata T, Takaishi H, Takito J, Hakozaki A, Furukawa M, Uchikawa S,Kimura T, Okada Y, Matsumoto M, Yoshimura A, Nishimura R, Reddy SV, Asahara H, Toyama Y
    • Journal Title

      Blood 113

      Pages: 2202-2212

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Signal transduction and transcriptional regulation during mesenchymal cell differentiation.2008

    • Author(s)
      Nishimura R, et al.
    • Journal Title

      J Bone Miner Metab 26

      Pages: 203-121

    • NAID

      10024457887

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Msx2 stimulates chondrocyte maturation by controlling lhh expression.2008

    • Author(s)
      Amano K, et al.
    • Journal Title

      J Biol Chem 283

      Pages: 29513-29521

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Paraspeckle protein p54^<nrb> links Sox9-mediated transcription with RNA processing during chondrogenesis in mice.2008

    • Author(s)
      Hata K, et al.
    • Journal Title

      J Clin Invest 118

      Pages: 3098-3108

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] OASIS, an endoplasmic reticulum stress transducer, is involved in bone formation.2010

    • Author(s)
      村上智彦, 中西雅子, 米田俊之, 池川志郎, 今泉和則
    • Organizer
      American Society for Biochemistry and Molecular Biology
    • Year and Date
      2010-04-26
    • Related Report
      2010 Final Research Report
  • [Presentation] Transcription factor Dmrt2, a downstream molecule of Sox 5/6/9, promotes late chondrogenesis as a linker between Sox5/6/9 and Runx2.2009

    • Author(s)
      Ono K, Hata K, Nakanishi M, Amano K, Nishimura R, Yoneda T
    • Organizer
      31st Annual Meeting of the American Society for Bone and Mineral Research
    • Year and Date
      2009-09-12
    • Related Report
      2010 Final Research Report
  • [Presentation] Transcription factor Dmrt2, a downsstream molecule of Sox 5/6/9, promotes late chondrogenesis as a linker between Sox5/6/9 and Runx2.2009

    • Author(s)
      Ono, et al.
    • Organizer
      American Society for Bone and Mineral Research
    • Place of Presentation
      アメリカ合衆国コロラド
    • Year and Date
      2009-09-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] The roles of ER stress transducer BBF2H7 in chondrogenesis.2009

    • Author(s)
      Hino S, Saito A, Nishimura R, Yoneda T, Ikegawa S, Imaizumi K
    • Organizer
      31st Annual Meeting of the American Society for Bone and Mineral Research
    • Year and Date
      2009-09-11
    • Related Report
      2010 Final Research Report
  • [Presentation] 小胞体膜貫通型転写因子OASIS と骨形成2009

    • Author(s)
      村上智彦、西村理行、米田俊之、古市達哉、和中明生、今泉和則
    • Organizer
      第27回日本骨代謝学会学術集会
    • Year and Date
      2009-07-24
    • Related Report
      2010 Final Research Report
  • [Presentation] Sox9 の標的転写因子Dmrt2 はRunx2 を介して内軟骨性骨化の後期分化を制御する2009

    • Author(s)
      小野孝一郎、波多賢二、中西雅子、西村理行、米田俊之
    • Organizer
      第27回日本骨代謝学会学術集会
    • Year and Date
      2009-07-23
    • Related Report
      2010 Final Research Report
  • [Presentation] 小胞体ストレス応答と軟骨形成2009

    • Author(s)
      斎藤敦、日野真一郎、西村理行、米田俊之、古市達哉、今泉和則
    • Organizer
      第27回日本骨代謝学会学術集会
    • Year and Date
      2009-07-23
    • Related Report
      2010 Final Research Report
  • [Presentation] 軟骨形成における小胞体ストレスセンサーBBF2H7 の役割2009

    • Author(s)
      齋藤敦, 日野真一郎, 西村理行, 米田俊之, 古市達哉, 池川志郎, 今泉和則
    • Organizer
      日本分子生物学会第9回春季シンポジウム
    • Year and Date
      2009-05-10
    • Related Report
      2010 Final Research Report
  • [Presentation] 小胞体ストレスセンサーOASIS による骨形成制御2009

    • Author(s)
      村上智彦、西村理行、米田俊之、池川志郎、和中明生,今泉和則
    • Organizer
      日本分子生物学会第9回春季シンポジウム
    • Year and Date
      2009-05-10
    • Related Report
      2010 Final Research Report
  • [Presentation] A transcription dactor Znf219 regulates chondrogenesis by forming a transcriotional factory complex with Sox9.2009

    • Author(s)
      Takigawa Y, Hata K, Muramatsu S, Amano K, Ono K, Takada K, WakabayashiM, Matsuda A, Nishimura R, Yoneda T
    • Organizer
      2^<nd> Joint Meeting of the International Bone & Mineral Society and the Australian & New Zealand Bone & Mineral Society.
    • Year and Date
      2009-03-22
    • Related Report
      2010 Final Research Report
  • [Presentation] Signal transduction and transcriptional regulation during skeletal cell differentiation2008

    • Author(s)
      Riko Nishimura
    • Organizer
      日本骨代謝学会学術集会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2008-10-31
    • Related Report
      2008 Annual Research Report
  • [Presentation] Sox9ファミリーはPTHrP の発現誘導を介し内軟骨性骨形成の後期分化を抑制する2008

    • Author(s)
      天野克比古、波多賢二、小野孝一郎、古郷幹彦、西村理行、米田俊之
    • Organizer
      第26回日本骨代謝学会
    • Year and Date
      2008-10-30
    • Related Report
      2010 Final Research Report
  • [Presentation] 転写制御因子Znf219 は、Sox9 転写ファクトリーの構成因子として軟骨細胞分化を制御する2008

    • Author(s)
      滝川陽子、波多賢二、村松周治、天野克比古、若林真、松田昭生、西村理行、米田俊之
    • Organizer
      第26回日本骨代謝学会
    • Year and Date
      2008-10-30
    • Related Report
      2010 Final Research Report
  • [Presentation] 性分化制御転写因子Dmrt2 は内軟骨性骨化を制御する2008

    • Author(s)
      小野孝一郎、波多賢二、杉田敦、天野克比古、滝川陽子、中西雅子、西村理行、米田俊之
    • Organizer
      第26回日本骨代謝学会
    • Year and Date
      2008-10-29
    • Related Report
      2010 Final Research Report
  • [Presentation] 骨吸収におけるproteininhibitor of activated STAT3 (PIAS3)の役割2008

    • Author(s)
      日方智宏、高石官成、滝戸二郎、箱崎彰裕、古川満、内川伸一、東門田誠一、依田昌樹、松本征仁、西村理行、松本守雄、戸山芳昭.
    • Organizer
      第26回日本骨代謝学会
    • Year and Date
      2008-10-29
    • Related Report
      2010 Final Research Report
  • [Presentation] 内軟骨性骨化過程における性分化制御転写因子Dmrt2 の役割2008

    • Author(s)
      中村恵理子、波多賢二、西村理行、米田俊之
    • Organizer
      第50回歯科基礎医学会
    • Year and Date
      2008-09-23
    • Related Report
      2010 Final Research Report
  • [Presentation] A Transcription Factor Znf219 Regulates Chondrocyte Differentiation Through Forming Transcription Factory Complex with Sox92008

    • Author(s)
      Takigawa Y, Hata K, Muramatsu S, Amano K, Takada K, Matsuda A, Nishimura R, Yoneda T
    • Organizer
      30th Annual Meeting of the American Society for Bone and Mineral Research
    • Year and Date
      2008-09-16
    • Related Report
      2010 Final Research Report
  • [Presentation] Transcription Factor Dmrt2 Controls Endochondral Ossification Through Regulating Type 10 Collagen (Col10a1) Gene Expression.2008

    • Author(s)
      Ono K, Hata K, Nakamura E, Sugita A, Amano K, Nakanishi M, Takigawa Y, Nishimura R, Takenoshita S, Yoneda T
    • Organizer
      30th Annual Meeting of the American Society for Bone and Mineral Research
    • Year and Date
      2008-09-13
    • Related Report
      2010 Final Research Report
  • [Book] 骨の分子生物学.口腔外科ハンドマニュアル'09 分担執筆2009

    • Author(s)
      米田俊之、西村理行
    • Publisher
      クインテッセンス株式会社
    • Related Report
      2010 Final Research Report
  • [Book] 骨の分子生物学 口腔外科ハンドマニュアル '092009

    • Author(s)
      米田俊之
    • Total Pages
      15
    • Publisher
      クインテッセンス株式会社
    • Related Report
      2009 Annual Research Report
  • [Book] 生命歯科医学のカッティング・エッジ2008

    • Author(s)
      西村 理行ら
    • Total Pages
      287
    • Publisher
      大阪大学出版会
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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