Signaling Crosstalk between PPARgamma and BMP2 in Mesenchymal Stem Cells.

• Project/Area Number: 23791662
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Keio University
• Principal Investigator: TAKADA Ichiro 慶應義塾大学, 医学部, 助教 (50361655)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 転写 / 間葉系幹細胞 / PPARγ / BMP2 / 骨芽細胞 / 脂肪細胞 / エピジェネティクス

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

• [Journal Article] Epigenetic Regulation of Adipogenesis by PHF2 Histone Demethylase (2013)
  • Author(s): Okuno Y
  • Journal Title: Diabetes Volume: in press Issue: 5 Pages: 1426-34
  • DOI: 10.2337/db12-0628
  • Peer Reviewed
• [Journal Article] Nuclear Receptors in Bone Physiology and Diseases (2013)
  • Author(s): Imai Y, Youn MY, Inoue K, Takada I, Kouzmenko A, Kato S
  • Journal Title: Physiol Rev Volume: 93(2) Issue: 2 Pages: 481-523
  • DOI: 10.1152/physrev.00008.2012
  • Peer Reviewed
• [Journal Article] Structural Features and Transcriptional Activity of Chicken PPARs (α, β, and γ). (2013)
  • Author(s): Takada I, Kobayashi M.
  • Journal Title: PPAR Research Volume: 2013 Pages: 186312-186312
  • 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 PPARγ and BMP2 in Mesenchymal Stem Cells. (2012)
  • Author(s): Takada I, Yogiashi Y, Kato S.
  • Journal Title: PPAR Research Volume: 2012 Pages: 607141-607141
  • DOI: 10.1155/2012/607141
  • Peer Reviewed
• [Journal Article] Peroxiredoxin family proteins are key initiators of post-ischemic inflammation in the brain (2012)
  • Author(s): Shichita T
  • Journal Title: Nature Medicine Volume: 18 Issue: 6 Pages: 911-917
  • 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 pathways (2012)
  • Author(s): Sugiyama Yuki, 他
  • Journal Title: International Immunology Volume: 24 Issue: 4 Pages: 253-256
  • DOI: 10.1093/intimm/dxr126
  • Peer Reviewed
• [Journal Article] Wnt5a-Ror2 signaling between osteoblasts and osteoclast precursors enhances osteoclastogenesis (2012)
  • 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, T.J., Minami, Y., Takahashi, N.
  • Journal Title: Nat.Med. Volume: (印刷中) Issue: 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-ss-Smad pathway (2011)
  • Author(s): Wakabayashi Yu, 他
  • Journal Title: Journal of Biological Chemistry Volume: 286 Issue: 41 Pages: 35456-35465
  • DOI: 10.1074/jbc.m111.236794
  • 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 pathway. (2011)
  • 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: Journal of Biological Chemistry Volume: 286 Pages: 35456-35465
  • Peer Reviewed
• [Presentation] Pericapillary Bone Formation by Mural Osteoblasts during Endochondral Ossification (2013)
  • 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] Pericapillary Bone Formation by Mural Osteoblasts during Endochondral Ossification (2013)
  • Author(s): Ichiro Takada*, Nobuhito Nango, Yoshihiro Takeda, Atsushi Momose, Yoshiaki Kubota, Sho Kanzaki, Kouji Shimoda, Yasunari Takada, Latifa Bakiri, Erwin Wagner, and Koichi Matsuo
  • Organizer: ASBMR
  • Place of Presentation: ボルチモア(アメリカ)
• [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 differentiation (2011)
  • 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
• [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(招待講演)
  • Place of Presentation: 淡路夢舞台国際会議場(兵庫)