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2013 Fiscal Year Final Research Report

Signaling Crosstalk between PPARgamma and BMP2 in Mesenchymal Stem Cells.

Research Project

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Project/Area Number 23791662
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Orthopaedic surgery
Research InstitutionKeio University

Principal Investigator

TAKADA Ichiro  慶應義塾大学, 医学部, 助教 (50361655)

Project Period (FY) 2011 – 2012
Keywords転写 / 間葉系幹細胞 / PPARγ / BMP2
Research Abstract

Recent studies have revealed that PPARgamma's transactivation function is regulated by extracellular signals. Among these factors, BMP2 strongly induces bone formation, but the effect of BMP2 on PPARgamma function remains unclear. We examined the effect of BMP2 and PPARgamma in ST2 cells and found that PPARgamma activation affected BMP2's signaling pathway through epigenetic regulation. Although BMP2 did not interfere with PPARgamma-mediated adipogenesis, BMP2 increased mRNA expression levels of PPARgamma target genes (such as Fabp4 and Nr1h3) when cells were first treated with troglitazone (TRO). Moreover, PPARgamma activation affected BMP2 through enhancement of histone activation markers (acetylated histone H3 and trimethylated Lys4 of histone H3) on the Runx2 promoter. These results suggest that the order of treatment with BMP2 and a PPARgamma ligand is critical for adipogenesis and osteoblastogenesis switching in MSCs.

  • Research Products

    (15 results)

All 2013 2012 2011

All Journal Article (10 results) (of which Peer Reviewed: 8 results) Presentation (5 results)

  • [Journal Article] Epigenetic regulation of adipogenesis by PHF2 histone demethylase2013

    • Author(s)
      Okuno Y, Ohtake F, Igarashi K, Kanno J, Matsumoto T, Takada I, Kato S, Imai Y
    • Journal Title

      Diabetes

      Volume: 62(5) Pages: 1426-34

    • DOI

      10.2337/db12-0628

    • Peer Reviewed
  • [Journal Article] Nuclear receptors in bone physiology and diseases2013

    • Author(s)
      Imai Y, Youn MY, Inoue K, Takada I, Kouzmenko A, Kato S
    • Journal Title

      Physiol Rev

      Volume: 93(2) Pages: 481-523

    • DOI

      10.1152/physrev.00008.2012

    • Peer Reviewed
  • [Journal Article] Structural Features and Transcriptional Activity of Chicken PPARs (α,β, andγ)2013

    • Author(s)
      Takada I, Kobayashi M
    • Journal Title

      PPAR Res

      Volume: 2013 Pages: 186312

    • DOI

      10.1155/2013/186312

    • Peer Reviewed
  • [Journal Article] PPAR系核内受容体と分子標的2012

    • Author(s)
      高田伊知郎、加藤茂明
    • Journal Title

      日本臨床2012年増刊号11月

      Volume: 70 Suppl 8 Pages: 251-5

  • [Journal Article] Signaling Crosstalk between PPARγand BMP2 in Mesenchymal Stem Cells2012

    • Author(s)
      Takada I, Yogiashi Y, Kato S
    • Journal Title

      PPAR Res

      Volume: 2012 Pages: 607141

    • DOI

      10.1155/2012/607141

    • Peer Reviewed
  • [Journal Article] Peroxiredoxin family proteins are key initiators of post-ischemic inflammation in the brain2012

    • Author(s)
      Shichita T, Hasegawa E, Kimura A, Morita R, Sakaguchi R, Takada I, Sekiya T, Ooboshi H, Kitazono T, Yanagawa T, Ishii T, Takahashi H, Mori S, Nishibori M, Kuroda K, Akira S, Miyake K, Yoshimura A
    • Journal Title

      Nat Med

      Volume: 18(6) Pages: 911-7

    • DOI

      10.1038/nm.2749

    • Peer Reviewed
  • [Journal Article] 骨芽細胞・脂肪細胞分化スイッチング2012

    • Author(s)
      高田伊知郎
    • Journal Title

      Clin Calcium

      Volume: 22(5)(CliCa1205629636) Pages: 629-36

  • [Journal Article] Smad2 and Smad3 are redundantly essential for the suppression of iNOS synthesis in macrophages by regulating IRF3 and STAT1 pathways2012

    • Author(s)
      Sugiyama Y, Kakoi K, Kimura A, Takada I, Kashiwagi I, Wakabayashi Y, Morita R, Nomura M, Yoshimura A
    • Journal Title

      Int Immunol

      Volume: 24(4) Pages: 253-65

    • DOI

      10.1093/intimm/dxr126

    • Peer Reviewed
  • [Journal Article] Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhances osteoclastogenesis2012

    • Author(s)
      Maeda K, Kobayashi Y, Udagawa N, Uehara S, Ishihara A, Mizoguchi T, Kikuchi Y, Takada I, Kato S, Kani S, Nishita M, Marumo K, Martin TJ, Minami Y, Takahashi N
    • Journal Title

      Nat Med

      Volume: 18(3) Pages: 405-12

    • DOI

      10.1038/nm.2653

    • Peer Reviewed
  • [Journal Article] Histone 3 lysine 9 (H3K9) methyltransferase recruitment to the interleukin-2 (IL-2) promoter is a mechanism of suppression of IL-2 transcription by the transforming growth factor-β-Smad pathway2011

    • Author(s)
      Wakabayashi Y, Tamiya T, Takada I, Fukaya T, Sugiyama Y, Inoue N, Kimura A, Morita R, Kashiwagi I, Takimoto T, Nomura M, Yoshimura A
    • Journal Title

      Histone 3 lysine 9 (H3K9) methyltransferase recruitment to the interleukin-2 (IL-2) promoter is a mechanism of suppression of IL-2 transcription by the transforming growth factor-β-Smad pathway

      Volume: 286(41) Pages: 35456-65

    • DOI

      10.1074/jbc.M111.236794

    • Peer Reviewed
  • [Presentation] Pericapillary Bone Formation by Mural Osteoblasts during Endochondral Ossification2013

    • Author(s)
      Ichiro Takada, et al
    • Organizer
      ASBMR
    • Place of Presentation
      Boltimore, USA(ポスター発表)
    • Year and Date
      2013-10-05
  • [Presentation] 骨芽細胞の可視化で見えたもの2013

    • Author(s)
      高田伊知郎
    • Organizer
      第3回超異分野学会
    • Place of Presentation
      東京(口頭発表)
    • Year and Date
      2013-02-16
  • [Presentation] 間葉系幹細胞における核内レセプターPPARγ活性制御シグナルの解析2012

    • Author(s)
      高田伊知郎
    • Organizer
      第二回奈良先端未来開拓コロキウム「シグナルの破綻による疾患の生物学」
    • Place of Presentation
      奈良、生駒(口頭発表)
    • Year and Date
      2012-12-04
  • [Presentation] 肥満におけるPPARγ活性制御シグナルWnt5aの機能解析2011

    • Author(s)
      高田伊知郎
    • Organizer
      第32回日本肥満学会
    • Place of Presentation
      兵庫、淡路(口頭発表)
    • Year and Date
      2011-09-23
  • [Presentation] Epigenetic control by TCR and TGF-βin T cell differentiation2011

    • Author(s)
      Ichiro Takada, et al
    • Organizer
      TNF 2011
    • Place of Presentation
      兵庫、淡路(口頭発表)
    • Year and Date
      2011-05-06

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Published: 2015-06-25  

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