• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

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

Research Project

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)
伊藤 公成  長崎大学, 医歯薬学総合研究科, 准教授 (00332726)
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
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥47,450,000 (Direct Cost: ¥36,500,000、Indirect Cost: ¥10,950,000)
Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2012: ¥13,130,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥3,030,000)
Fiscal Year 2011: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
Fiscal Year 2010: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
KeywordsRunx2 / エンハンサー / 骨芽細胞 / 転写制御 / 間葉系幹細胞 / Dlx5 / Mef2 / クロマチン修飾 / トランスジェニックマウス / FGF / Wnt / Tcf7 / 骨格形成 / 軟骨細胞 / 転写因子
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.

Report

(5 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (56 results)

All 2014 2013 2012 2011 2010 Other

All Journal Article (36 results) (of which Peer Reviewed: 34 results,  Open Access: 2 results) Presentation (17 results) (of which Invited: 3 results) Remarks (2 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) Issue: 1 Pages: 86629-86629

    • DOI

      10.1371/journal.pone.0086629

    • NAID

      120006987119

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [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

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dlx5 and Mef2 Regulate a Novel Runx2 Enhancer for Osteoblast-Specific Expression.2014

    • Author(s)
      Kawane T, Komori H, Liu W, Moriishi T, Miyazaki T, Mori M, Matsuo Y, Takada Y, Izumi S, Jiang Q, Nishimura R, Kawai Y, Komori T.
    • Journal Title

      Journal of bone and mineral research

      Volume: - Issue: 9 Pages: 1960-1969

    • DOI

      10.1002/jbmr.2240

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Filamin-interacting proteins, Cfm1 and Cfm2, are essential for the formation of cartilaginous skeletal elements.2014

    • Author(s)
      Mizuhashi K, Kanamoto T, Moriishi T, Muranishi Y, Miyazaki T, Terada K, Omori Y, Ito M, Komori T, Furukawa T.
    • Journal Title

      Human molecular genetics

      Volume: - Issue: 11 Pages: 2953-2967

    • DOI

      10.1093/hmg/ddu007

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [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

    • Related Report
      2013 Final Research Report
    • 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) Issue: 1 Pages: 1003132-1003132

    • DOI

      10.1371/journal.pgen.1003132

    • NAID

      120006985752

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Thrombospondin-1 is a putative target gene of runx2 and runx3.2013

    • Author(s)
      Shi X, Deepak V, Wang L, Ba X, Komori T, Zeng X, Liu W.
    • Journal Title

      International journal of molecular sciences [electronic resource]

      Volume: 14 Issue: 7 Pages: 14321-14332

    • DOI

      10.3390/ijms140714321

    • NAID

      120006986154

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pin1-mediated Runx2 modification is critical for skeletal development.2013

    • Author(s)
      Yoon WJ, Islam R, Cho YD, Woo KM, Baek JH, Uchida T, Komori T, van Wijnen A,Stein JL, Lian JB, Stein GS, Choi JY, Bae SC, Ryoo HM.
    • Journal Title

      Journal of cellular physiology

      Volume: 228 Issue: 12 Pages: 2377-2385

    • DOI

      10.1002/jcp.24403

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel sandwich ELISAs for rat DMP1: age-related decrease of circulatory DMP1 levels in male rats.2013

    • Author(s)
      Sato S, Hashimoto J, Usami Y, Ohyama K, Isogai Y, Hagiwara Y, Maruyama N, Komori T, Kuroda T, Toyosawa S.
    • Journal Title

      Bone

      Volume: 57 Issue: 2 Pages: 429-436

    • DOI

      10.1016/j.bone.2013.09.013

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of Rb family proteins by Cdk6/Ccnd1 in growth plates.2013

    • Author(s)
      Komori T
    • Journal Title

      Cell Cycle

      Volume: 12 Issue: 14 Pages: 2161-2162

    • DOI

      10.4161/cc.25515

    • NAID

      120006986153

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Overexpression of Cdk6 and Ccnd1 in chondrocytes inhibited chondrocyte maturation and caused p53dependent apoptosis without enhancing proliferation.2013

    • 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: 33 Issue: 14 Pages: 1862-1871

    • DOI

      10.1038/onc.2013.130

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functions of the osteocyte network in the regulation of bone mass.2013

    • Author(s)
      Komori T
    • Journal Title

      Cell and tissue research

      Volume: 352 Issue: 2 Pages: 191-198

    • DOI

      10.1007/s00441-012-1546-x

    • NAID

      120006986155

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Galnt3 deficiency disrupts acrosome formation and leads to oligoasthenoteratozoos permia2013

    • Author(s)
      宮崎 敏博
    • Journal Title

      Histochemistry and Cell Biology

      Volume: 139 Issue: 2 Pages: 339-354

    • DOI

      10.1007/s00418-012-1031-3

    • Related Report
      2012 Annual Research Report
    • 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) Issue: 6 Pages: 40143-40143

    • DOI

      10.1371/journal.pone.0040143

    • NAID

      120006985704

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • 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

    • Related Report
      2013 Final Research Report
    • 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) Issue: 3 Pages: e32364-e32364

    • DOI

      10.1371/journal.pone.0032364

    • NAID

      120006985432

    • Related Report
      2013 Final Research Report
    • 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

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] In situ differentiation of CD8ααT cells from CD4T cells in peripheral lymphoid tissues.2012

    • Author(s)
      Nambu Y
    • Journal Title

      Scientific reports

      Volume: 2 Pages: 642-642

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chronological histological changes during bone regeneration on a non-crosslinked atelocollagen matrix.2012

    • Author(s)
      Kagawa R
    • Journal Title

      Journal of bone and mineral metabolism

      Volume: 30 Issue: 6 Pages: 638-650

    • DOI

      10.1007/s00774-012-0376-y

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interaction of Tmem119 and the bone morphogenetic protein pathway in the commitment of myoblastic into osteoblastic cells.2012

    • Author(s)
      Tanaka K
    • Journal Title

      Bone

      Volume: 51 Issue: 1 Pages: 158-167

    • DOI

      10.1016/j.bone.2012.04.017

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Calcium/calmodulin-signaling supports TRPV4 activation in osteoclasts and regulates bone mass.2012

    • Author(s)
      Masuyama R
    • Journal Title

      Journal of bone and mineral research

      Volume: 27 Issue: 8 Pages: 1708-1721

    • DOI

      10.1002/jbmr.1629

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] OBIF, an osteoblast induction factor, plays an essential role in bone formation in association with osteoblastogenesis2012

    • Author(s)
      Mizuhashi K
    • Journal Title

      Development, growth and differentiation

      Volume: 54 Issue: 4 Pages: 474-480

    • DOI

      10.1111/j.1440-169x.2012.01333.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SP7 inhibits osteoblast differentiation at a late stage in mice2012

    • Author(s)
      Yoshida CA
    • Journal Title

      PLoS One

      Volume: 7巻

    • Related Report
      2011 Annual Research Report
    • 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) Issue: 11 Pages: e27487-e27487

    • DOI

      10.1371/journal.pone.0027487

    • NAID

      120006985216

    • Related Report
      2013 Final Research Report
    • 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

    • Related Report
      2013 Final Research Report
    • 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

    • NAID

      10029024664

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of bcl2 in osteoblasts inhibits osteoblast differentiation and induces osteocyte apoptosis2011

    • Author(s)
      Moriishi T
    • Journal Title

      PLoS One

      Volume: 6巻

    • NAID

      120006985216

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Early onset of Runx2 expression caused craniosynostosis, ectopic bone formation, and limb defects2011

    • Author(s)
      Maeno T
    • Journal Title

      Bone

      Volume: 49巻 Pages: 673-682

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pyruvate dehydrogenase kinase 4 induces bone loss at unloading by promoting osteoclastogenesis2011

    • Author(s)
      Wang Y
    • Journal Title

      Bone

      Volume: 50巻 Pages: 409-419

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparative morphology of the osteocyte lacunocanalicular system in various vertebrates2011

    • Author(s)
      Cao L
    • Journal Title

      Journal of bone and mineral metabolism

      Volume: 29巻 Pages: 662-670

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of Tcf7 by Runx2 in chondrocyte maturation and proliferation2011

    • Author(s)
      Mikasa M
    • Journal Title

      Journal of bone and mineral metabolism

      Volume: 29巻 Pages: 291-299

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Signaling networks in RUNX2-dependent bone development.2011

    • Author(s)
      Komori T
    • Journal Title

      Journal of Cellular Biochemistry

      Volume: 112 Pages: 750-755

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Parathyroid Hormone-responsive Smad3-related Factor, Tmem 119, Promotes Osteoblast Differentiation and Interacts with the Bone Morphogenetic Protein-Runx2 Pathway.2011

    • Author(s)
      Hisa I
    • Journal Title

      Journal of Biological Chemistry

      Volume: 286 Pages: 9787-9796

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of Notch1 signaling by Runx2 during osteoblast differentiation.2011

    • Author(s)
      Ann EJ
    • Journal Title

      Journal of Bone and Mineral Research

      Volume: 26 Pages: 317-330

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of Tcf7 by Runx2 in chondrocyte maturation and proliferation.2010

    • Author(s)
      Mikasa M
    • Journal Title

      Journal of Bone and Mineral Metabolism

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of osteoblast differentiation by runx2.2010

    • Author(s)
      Komori T
    • Journal Title

      Advances in Experimental Medicine and Biology

      Volume: 658 Pages: 43-49

    • Related Report
      2010 Annual Research Report
  • [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)
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [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)
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Osteocyte network and mechanical stress.2013

    • Author(s)
      Toshihisa Komori
    • Organizer
      The 22nd International Rheumatology Symposium
    • Place of Presentation
      京都市 国立京都国際会館
    • Related Report
      2013 Annual Research Report
  • [Presentation] Osteocytes, Coordinator of the Bone.2013

    • Author(s)
      Toshihisa Komori
    • Organizer
      2013 Seoul International Congress of Endocrinology and Metabolism
    • Place of Presentation
      Grand Hilton Seoul Hotel, Korea
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Proliferation, differentiation, and apoptosis in chondrocyte.2013

    • Author(s)
      Toshihisa Komori
    • Organizer
      2013 Seoul International Congress of Endocrinology and Metabolism
    • Place of Presentation
      Grand Hilton Seoul Hotel, Korea
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Roles of Cbfb in bone development during embryonic stage and after birth.2013

    • Author(s)
      Toshihisa Komori
    • Organizer
      The EMBO Workshop RUNX transcription factors in development and disease
    • Place of Presentation
      Wilsede,Germany
    • Related Report
      2013 Annual Research Report
  • [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
      岡山市 岡山コンベンションセンター
    • Related Report
      2013 Annual Research Report
  • [Presentation] 骨芽細胞分化および血管新生におけるSp7の役割2013

    • Author(s)
      小守寿人、小守壽文
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸市 神戸ポートアイランド
    • Related Report
      2013 Annual Research Report
  • [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
    • Related Report
      2013 Final Research Report
  • [Presentation] Regulation of bone mass at unloaded condition by 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
    • Year and Date
      2011-11-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] PDK4は骨粗鬆症の破骨細胞分化を促進する2011

    • Author(s)
      王宇英
    • Organizer
      第53回歯科基礎医学会学術大会・総会
    • Place of Presentation
      長良川国際会議場
    • Year and Date
      2011-10-02
    • Related Report
      2011 Annual Research Report
  • [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)
    • Related Report
      2013 Final Research Report
  • [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)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 骨芽細胞分化と血管新生2010

    • Author(s)
      小守壽文
    • Organizer
      第28回骨代謝学会学術集会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 骨芽細胞分化における抗アポトーシス分子Bcl-2の役割2010

    • Author(s)
      森石武史
    • Organizer
      第28回骨代謝学会学術集会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Runx2 and FGF Signaling2010

    • Author(s)
      小守壽文
    • Organizer
      第58回国際歯科研究学会日本部会(JADR)総会・学術大会
    • Place of Presentation
      九州歯科大学キャンパス(福岡県)
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2013 Final Research Report
  • [Remarks] 長崎大学細胞生物学分野ホームページ

    • URL

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

    • Related Report
      2013 Annual Research Report
  • [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
      2011-138935
    • Filing Date
      2011-06-22
    • Related Report
      2013 Final Research Report 2011 Annual Research Report

URL: 

Published: 2010-08-23   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi