Identification and functional analysis of novel Osterix-inducible osteoblast differentiation accelerators

• Project/Area Number: 19390401
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Japanese Foundation For Cancer Research
• Principal Investigator: MAEDA Shingo Japanese Foundation For Cancer Research, 癌研究所生化学部, 研究員 (60353463)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2008: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000); Fiscal Year 2007: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
• Keywords: 骨 / 軟骨代謝学 / オステリクス / 骨芽細胞 / BMP / Osterix

Research Abstract

骨を造る骨芽細胞は未分化前駆細胞においてRunx2の発現で分化が決定し、転写因子Osterixの誘導を境に分化成熟が進む。ところがなぜOsterixが無ければ骨芽細胞分化が進まないのかは不明な点が多く残されている。我々はOsterixと骨形成蛋白(BMP)で誘導される未知の標的遺伝子がOsterixの骨芽細胞分化における機能に重要な役割を果たしていると仮定し、マイクロアレイ技術を用いて検索した。その結果候補遺伝子としてPitx2、Hesr1、そして機能未知の膜蛋白が同定された。Pitx2がOsterixの発現抑制を介して骨芽細胞分化を負に制御する事、Hesr1がファミリー分子のHesr3と協調的に骨芽細胞におけるオステオプロテジェリン(Opg)の発現促進を介して破骨細胞分化を負に制御する事、Osterixで誘導される機能未知の膜蛋白質が骨形成に重要な役割を演じる事を解明した

Research Products

• [Journal Article] Arkadia represses the expression of myoblast differentiation markers through degradation of Ski and the Ski-bound Smad complex in C2C12 myoblasts (2009)
  • Author(s): Yuzawa H, Koinuma D, Maeda S, Yamamoto K, Miyazawa K, Imamura T
  • Journal Title: Bone 44 Pages: 53-60
  • Peer Reviewed
• [Journal Article] Expression of osterix inhibits bone morphogenetic protein-induced chondrogenic differentiation of mesenchymal progenitor cells (2009)
  • Author(s): Tominaga H, Maeda S (corresponding author), Miyoshi H, Miyazono K, Komiya S, Imamura T
  • Journal Title: J Bone Miner Metab 27 Pages: 36-45
  • NAID: 10025336129
  • Peer Reviewed
• [Journal Article] Expression of osterix inhibits bone morphogenetic protein-induced chondrogenic differentiation of mesenchymal progenitor cells (2009)
  • Author(s): Tominaga H., Maeda S. (corre sponding author), et al.
  • Journal Title: Journal of Bone and Mineral Metabolism 27 Pages: 36-45
  • NAID: 10025336129
  • Peer Reviewed
• [Journal Article] Arkadia represses the expression of myoblast differentiation markers through degradation of Ski and the Ski-bound Smad complex in C2C12 myoblasts (2009)
  • Author(s): Yuzawa H., et al.
  • Journal Title: Bone 44 Pages: 53-60
  • Peer Reviewed
• [Journal Article] CCAAT/enhancer-binding protein β promotes osteoblast differentiation by enhancing Runx2 activity with ATF4 (2008)
  • Author(s): Tominaga H, Maeda S (corresponding author), Hayashi M, Takeda S, Akira S, Komiya S, Nakamura T, Akiyama H, Imamura T
  • Journal Title: Mol Biol Cell 19 Pages: 5373-5386
  • Peer Reviewed
• [Journal Article] Pitx2 prevents osteoblastic transdifferentiation of myoblasts by bone morphogenetic proteins (2008)
  • Author(s): Hayashi M, Maeda S (corresponding author), Aburatani H, Kitamura K, Miyoshi H, Miyazono K, Imamura T
  • Journal Title: J Biol Chem 283 Pages: 565-571
  • Peer Reviewed
• [Journal Article] CCAAT/enhancer-binding protein β promotes osteoblast differentiation by enhancing Runx2 activity with ATF4 (2008)
  • Author(s): Tominaga H., Maeda S. (corre sponding author), et al.
  • Journal Title: Molecular Biology of the Cell 19 Pages: 5373-5386
  • Peer Reviewed
• [Journal Article] Pitx2 prevents osteoblastic transdifferentiation of myoblasts by bone morphogenetic proteins (2008)
  • Author(s): Hayashi M, Maeda S(corresponding author), et. al.
  • Journal Title: Journal of Biological Chemistry 283 Pages: 565-571
  • Peer Reviewed
• [Presentation] Hesr1とHesr3は骨芽細胞のOsteoprotegerin発現促進を介して骨吸収を制御し骨量を維持する (2008)
  • Author(s): 前田真吾
  • Organizer: 第26回日本骨代謝学会
  • Place of Presentation: 大阪市、大阪国際会議場
  • Year and Date: 2008-10-29
• [Presentation] Hesr1とHesr3は骨芽細胞の Osteoprotegerin 発現促進を介して骨吸収を制御し骨量を維持する (2008)
  • Author(s): 前田真吾
  • Organizer: 第26回日本骨代謝学会
  • Place of Presentation: 大阪市大阪国際会議場
  • Year and Date: 2008-10-29
• [Presentation] Hesr1とHesr3は相補的に骨芽細胞分化・骨量を制御する (2007)
  • Author(s): 前田真吾、小久保博樹、油谷浩幸、小宮節郎、宮園浩平
  • Organizer: BMB2007(第30回日本分子生物学会・第80回日本生化学会大会合同大会)
  • Place of Presentation: 横浜市
  • Year and Date: 2007-12-12
• [Presentation] Hey1とHeyLは相補的に骨芽細胞分化を制御する (2007)
  • Author(s): 前田真吾、小久保博樹、小宮節郎、宮園浩平、今村健志
  • Organizer: 第22回日本整形外科学会基礎学術集会
  • Place of Presentation: 浜松市
  • Year and Date: 2007-10-26
• [Presentation] 新規骨芽細胞分化制御因子の検索と解析 (2007)
  • Author(s): 前田 真吾
  • Organizer: 第4回「骨と関飾の代謝調節を考える基礎の会」
  • Place of Presentation: 千葉県木更津市
  • Year and Date: 2007-09-30
• [Presentation] Endogenous Hesr/Hey genes redundantly support osteoblast differentiation (2007)
  • Author(s): Shingo Maeda, Hiroki Kokubo, Hiroyuki Aburatani, Shintaro Nomura, Setsuro Komiya, Kohei Miyazono, Takeshi Imamura
  • Organizer: 第29回アメリカ骨代謝学会
  • Place of Presentation: ホノルル市、ハワイ州、アメリカ合衆国
  • Year and Date: 2007-09-19
• [Remarks]
  • URL: http://www.jfrc.or.jp/laboratory/tci/biochemistry/index.html
• [Remarks]
  • URL: http://www.jfcr.or.jp/laboratory/tci/biochemistry/index.html