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2013 Fiscal Year Final Research Report

The mechanism of transcriptional regulation of Runx2 gene and the program of skeletal development

Research Project

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Project/Area Number 22249062
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionNagasaki University

Principal Investigator

KOMORI Toshihisa  長崎大学, 医歯(薬)学総合研究科, 教授 (00252677)

Co-Investigator(Kenkyū-buntansha) HAYASHI Hideki  長崎大学, 大学院医歯薬学総合研究科, 准教授 (10218589)
MASUYAMA Ritsuko  長崎大学, 大学院医歯薬学総合研究科, 准教授 (60297596)
Co-Investigator(Renkei-kenkyūsha) MIYAZAKI Toshihiro  長崎大学, 大学院医歯薬学総合研究科, 准教授 (10174161)
MORIISHI Takeshi  長崎大学, 大学院医歯薬学総合研究科, 助教 (20380983)
Project Period (FY) 2010-04-01 – 2014-03-31
KeywordsRunx2 / エンハンサー / 骨芽細胞 / 転写制御 / 間葉系幹細胞
Research Abstract

Runx2 is an essential transcription factor for osteoblast differentiation at an early stage and chondrocyte differentiation at a late stage. To elucidate the mechanism of the transcriptional regulation of Runx2 gene, we generated GFP transgenic mice using the BAC clone of Runx2 gene locus. By deleting the BAC clone, we identified osteoblast-specific enhancer. The enhancer directed GFP expression specifically to osteoblasts. Dlx5/Dlx6, Mef2, Tcf7, Ctnnb1, Sp7, Smad1, and Sox5/Sox6, which localized on the enhancer region, synergistically upregulated the enhancer activity. Dlx5 and Mef2 directly bound to the enhancer, while the other factors bound to the enhancer by protein-protein interaction. Thus, Dlx5/Dlx6 and Mef2, which formed an enhanceosome with Tcf7, Ctnnb1, Sp7, Smad1, and Sox5/Sox6, play an essential role in the osteoblast-specific activation of the enhancer, leading to the differentiation of mesenchymal stem cells to osteoblasts.

  • Research Products

    (18 results)

All 2014 2013 2012 2011 2010 Other

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (5 results) (of which Invited: 1 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Bcl2 deficiency activates FoxO through Akt inactivation and accelerates osteoblast differentiation2014

    • Author(s)
      Moriishi T, Kawai Y, Komori H, Rokutanda S, Eguchi Y, Tsujimoto Y, Asahina I, Komori T
    • Journal Title

      PLoS One

      Volume: 9(1) Pages: e86629

    • DOI

      10.1371/journal.pone.0086629

    • Peer Reviewed
  • [Journal Article] Filamin-interacting proteins, Cfm1 and Cfm2, are essential for the formation of cartilaginous skeletal elements2014

    • Author(s)
      Mizuhashi K, Komori T, Furukawa, T (他7名)
    • Journal Title

      Hum Mol Genet

      Volume: Vol.23 Pages: 2953-2967

    • Peer Reviewed
  • [Journal Article] Overexpression of Cdk6 and Ccnd1 in chondrocytes inhibited chondrocyte maturation and caused p53dependent apoptosis without enhancing proliferation2013

    • Author(s)
      Ito K, Maruyama Z, Sakai A, Izumi S, Moriishi T, Yoshida CA, Miyazaki T, Komori H, Takada K, Kawaguchi H, Komori T
    • Journal Title

      Oncogene

      Volume: Vol.33 Pages: 1862-1871

    • Peer Reviewed
  • [Journal Article] MAML1 enhances the transcriptional activity of Runx2 and plays a role in bone development2013

    • Author(s)
      Watanabe T, Komori T, Asahara H (他10名)
    • Journal Title

      PLos Genet

      Volume: 9(1) Pages: e1003132

    • DOI

      10.1371/journal.pgen.1003132

    • Peer Reviewed
  • [Journal Article] Osteocyte network; a negative regulatory system for bone mass augmented by the induction of Rankl in osteoblasts and Sost in osteocytes at unloading2012

    • Author(s)
      Moriishi T, Fukuyama R, Ito M, Miyazaki T, Maeno T, Kawai Y, Komori H, Komori T
    • Journal Title

      PLoS One

      Volume: 7(6) Pages: e40143

    • DOI

      10.1371/journal.pone.0040143

    • Peer Reviewed
  • [Journal Article] Calcium/calmodulin-signaling supports TRPV4 activation in osteoclasts and regulates bone mass2012

    • Author(s)
      Masuyama R, Mizuno A, Komori H, Kajiya H, Uekawa A, Kitaura H, Okabe K, Ohyama K, Komori T
    • Journal Title

      J Bone Miner Res

      Volume: Vol.27 Pages: 1708-1721

    • Peer Reviewed
  • [Journal Article] SP7 inhibits osteoblast differentiation at a late stage in mice2012

    • Author(s)
      Yoshida CA, Takada K, Komori T (他13名)
    • Journal Title

      PLoS One

      Volume: 7(3) Pages: e32364

    • DOI

      10.1371/journal.pone.0032364

    • Peer Reviewed
  • [Journal Article] Pyruvate dehydrogenase kinase 4 induces bone loss at unloading by promoting osteoclastogenesis2012

    • Author(s)
      Wang Y, Masuyama R, Komori T (他12名)
    • Journal Title

      Bone

      Volume: Vol.50 Pages: 409-419

    • Peer Reviewed
  • [Journal Article] Overexpression of bcl2 in osteoblasts inhibits osteoblast differentiation and induces osteocyte apoptosis2011

    • Author(s)
      Moriishi T, Masuyama R, Komori T (他11名)
    • Journal Title

      PLoS One

      Volume: 6(11) Pages: e27487

    • DOI

      10.1371/journal.pone.0027487

    • Peer Reviewed
  • [Journal Article] Early onset of Runx2 expression caused craniosynostosis, ectopic bone formation, and limb defects2011

    • Author(s)
      Maeno T, Moriishi T, Yoshida CA, Komori H, Kanatani N, Izumi S, Takaoka K, Komori T
    • Journal Title

      Bone

      Volume: Vol.49 Pages: 673-682

    • Peer Reviewed
  • [Journal Article] Regulation of Tcf7 by Runx2 in chondrocyte maturation and proliferation2011

    • Author(s)
      Mikasa M, Rokutanda S, Komori H, Ito K, Tsang YS, Date Y, Yoshida CA, Komori T
    • Journal Title

      J Bone Miner Metab

      Volume: Vol.29 Pages: 291-299

    • Peer Reviewed
  • [Presentation] 骨細胞ネットワークによるメカニカルストレス応答2013

    • Author(s)
      小守壽文
    • Organizer
      第55回歯科基礎医学会学術大会・総会
    • Place of Presentation
      岡山コンベンションセンター(岡山県)
    • Year and Date
      20130920-22
  • [Presentation] Roles of Cbfb in bone development during embryonic stage and after birth2013

    • Author(s)
      小守壽文
    • Organizer
      The EMBO Workshop RUNX transcription factors in development and disease
    • Place of Presentation
      Wilsede,Germany
    • Year and Date
      20130616-19
  • [Presentation] Osteocyte network and mechanical stress2013

    • Author(s)
      小守壽文
    • Organizer
      第22回国際リウマチシンポジウム
    • Place of Presentation
      国立京都国際会館(京都府)
    • Year and Date
      20130418-20
    • Invited
  • [Presentation] Regulation of Bone Mass through an Osteocyte Network2011

    • Author(s)
      小守壽文
    • Organizer
      1st Bio-Rheumatology International Congress
    • Place of Presentation
      ヒルトン東京ベイ(東京都)
    • Year and Date
      2011-11-15
  • [Presentation] Regulation of osteoblast differentiation and bone angiogenesis by RUNX2 and SP72010

    • Author(s)
      小守壽文
    • Organizer
      第17回国際RUNX ワークショップ
    • Place of Presentation
      オリエンタルホテル広島(広島県)
    • Year and Date
      20100711-14
  • [Remarks]

    • URL

      http://www.de.nagasaki-u.ac.jp/dokuji/kaibou-2/index.html

  • [Patent(Industrial Property Rights)] 荷重感知遺伝子2011

    • Inventor(s)
      小守壽文
    • Industrial Property Rights Holder
      長崎大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      特願2011-138935
    • Filing Date
      2011-06-22

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Published: 2015-06-25   Modified: 2015-07-02  

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