Understanding of molecular basis by which Indian hedgehog signaling regulates osteoblast differentiation

2009 Fiscal Year Final Research Report

• Project/Area Number: 19390473
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Osaka University
• Principal Investigator: NISHIMURA Riko Osaka University, 大学院・歯学研究科, 准教授 (60294112)
• Co-Investigator(Kenkyū-buntansha): YONEDA Toshiyuki 大阪大学, 大学院・歯学研究科, 教授 (80142313) ; HATA Kenji 大阪大学, 大学院・歯学研究科, 助教 (80444496)
• Project Period (FY): 2007 – 2009
• Keywords: 骨芽細胞 / 未分化間葉系細胞 / 骨形成 / インディアンヘッジホッグ / 細胞内シグナリング / 転写因子 / PTHrP

Research Abstract

Indian hedgehog (Ihh) has been shown to play important roles in development of several tissues including skeletal tissues. In particular, Ihh conducts bone formation by regulating osteoblast and chondrocyte differentiation. In this study, to understand the mechanisms of Ihh, we investigated mechanisms and roles of Ihh signaling pathway. We found that Ihh controls expression and function of transcription factors, Gli family members, thereby regulating osteoblast differentiation. Furthermore, we demonstrated that Ihh signaling collaborates with Bone morphogenetic protein 2 (BMP2) signaling and Runx2, and that this cross-talk enhances osteoblast differentiation.

Research Products

• [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
  • 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
  • Peer Reviewed
• [Journal Article] A Novel Role for TGF-・1 in Bone Remodeling. (2009)
  • Author(s): Nishimura R
  • Journal Title: IBMS BoneKey 6 Pages: 434-438
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Phenotypic analysis of Dlx5 overexpression in post-natal bone. (2008)
  • Author(s): Zhang J, Zhu J, Valverde P, Li L, Pageau S, Tu Q, Nishimura R, Yoneda T, Yang P, Zheng W, Ma W, Chen J
  • Journal Title: J Dent Res 87 Pages: 45-50
  • 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
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] Ihh/Gli2 signaling promotes osteoblast differentiation by regulating Runx2 expression and function. (2007)
  • Author(s): Shimoyama A, Wada M, Ikeda F, Hata K, Matsubara T, Nifuji A, Noda M, Amano K, Yamaguchi A, Nishimura R, Yoneda T
  • Journal Title: Mol Biol Cell 18 Pages: 2411-2418
  • Peer Reviewed
• [Journal Article] Functional gene screening system identified TRPV4 as a regulator of chondrogenic differentiation (2007)
  • Author(s): Muramatsu S, Wakabayashi M, Ohno T, Amano K, Ooishi K, Sugahara T, Shiojiri S, Tashiro K, Suzuki Y, Nishimura R, Kuhara S, Sugano S, Yoneda T, Matsuda A
  • Journal Title: J Biol Chem 282 Pages: 32158-67
  • Peer Reviewed
• [Presentation] A transcription dactor Znf219 regulates chondrogenesis by forming a transcriptional factory complex with Sox9. (2009)
  • Author(s): Takigawa Y, Hata K, Muramatsu S, Amano K, Ono K, Takada K, Wakabayashi M, Matsuda A, Nishimura R, Yoneda T
  • Organizer: 2nd Joint Meeting of the International Bone & Mineral Society and the Australian & New Zealand Bone & Mineral Society
  • Place of Presentation: Sydney
  • Year and Date: 20090000
• [Presentation] βTrcp1 Ubiquitin Complex Regulates Ihh-promoted Osteoblast Differentiation Through Gli2 Ubiquitination. (2007)
  • Author(s): Wada M, Matsubara T, Hata K, Imamura T, Nishimura R, Yoneda T
  • Organizer: The 29th American Society for Bone and Mineral Research.
  • Place of Presentation: Honolulu
  • Year and Date: 20070000
• [Presentation] Msx2 Promotes Late Stages of Chondrocyte Differentiation by Up-regulating Ihh Expression. (2007)
  • Author(s): Amano K, Ichida F, Sugita A, Hata K, Kogo M, Nishimura R, Yoneda T
  • Organizer: The 29th American Society for Bone and Mineral Research
  • Place of Presentation: Honolulu
  • Year and Date: 20070000
• [Presentation] Osterix Functions as Downstream of Runx2 and Msx2 During BMP2-Regulated Osteoblastogenesis. (2007)
  • Author(s): Matsubara T, Kumiko K, Hata K, Yamaguchi A, Aburatani H, Nishimura R, Yoneda T
  • Organizer: The 29th American Society for Bone and Mineral Research.
  • Place of Presentation: Honolulu
  • Year and Date: 20070000
• [Book] 「骨の分子生物学」, 「口腔外科ハンドマニュアル」 (2009)
  • Author(s): 米田俊之、西村理行
  • Total Pages: 23-37,291
  • Publisher: クインテッセンス出版
• [Book] 「分子生物硬組織研究のイノベーション」, 「生命歯科医学のカッティング・エッジ」 (2008)
  • Author(s): 西村理行、齋藤正寛、波多賢二、米田俊之
  • Total Pages: 287,2-23
  • Publisher: 大阪大学出版会