Analysis of cartilage formation and differentiation through regulation of chondrocyte signaling and transcription of matrix genes

2008 Fiscal Year Final Research Report

• Project/Area Number: 18390415
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Osaka University
• Principal Investigator: TSUMAKI Noriyuki Osaka University, 医学系研究科, 独立准教授 (50303938)
• Co-Investigator(Kenkyū-buntansha): YOSIKAWA Hideki 大阪大学, 医学系研究科, 教授 (60191558)
• Project Period (FY): 2006 – 2008
• Keywords: 内軟骨性骨化 / 軟骨発生 / 骨形成因子 / トランスジェニックマウス

Research Abstract

軟骨細胞分化におけるBMPシグナルの役割を詳細に解析するために、Smad7を軟骨細胞分化の各段階で過剰発現させるconditional transgenic mouseシステムを開発し、解析した。その結果、Smad7は軟骨形成阻害し、その原因として、BMPによって活性化されるMAPK経路のSmad7による抑制が示唆された。また、軟骨コラーゲン遺伝子のエピジェネティックな転写制御のメカニズムについてはXI型コラーゲン遺伝子のプロモーター領域にインシュレーターを発見し、ゲノム上の隣接遺伝子の転写制御に関与していることを明らかにした。

Research Products

• [Journal Article] Smad7 Inhibits Chondrocyte Differentiation at Multiple Steps during Endochondral Bone Formation and Down-regulates p38 MAPK Pathways. (2008)
  • Author(s): Iwai, T., Murai, J., Yoshikawa, H., Tsumaki, N.
  • Journal Title: J Biol Chem 283 Pages: 27154-27164
  • Peer Reviewed
• [Journal Article] Insulation of the Ubiquitous Rxrb Promoter from the Cartilage-specific Adjacent Gene Col11a2. (2008)
  • Author(s): Murai, J., Ikegami, D., Okamoto, M., Yoshikawa, H., Tsumaki, N.
  • Journal Title: J Biol Chem 283 Pages: 27677-27687
  • Peer Reviewed
• [Journal Article] Characteristics of fracture and related factors in patients with rheumatoid arthritis. (2008)
  • Author(s): Nampei, A., Hashimoto, J., Koyanagi, J., Ono, T., Hashimoto, H., Tsumaki, N., Tomita, T., Sugamoto, K., Nishimoto, N., Ochi, T., Yoshikawa, H.
  • Journal Title: Mod Rheumatol 18 Pages: 170-176
  • Peer Reviewed
• [Journal Article] Low-intensity pulsed ultrasound increases bone ingrowth into porous hydroxyapatite ceramic. (2007)
  • Author(s): Iwai, T., Harada, Y., Imura, K., Iwabuchi, S., Murai, J., Hiramatsu, K., Myoui, A., Yoshikawa, H., Tsumaki, N.
  • Journal Title: J Bone Miner Metab 25 Pages: 392-399
  • Peer Reviewed
• [Journal Article] Hyaline cartilage formation and enchondral ossification modeled with KUM5 and OP9 chondroblasts. (2007)
  • Author(s): Sugiki, T., Uyama, T., Toyoda, M., Morioka, H., Kume, S., Miyado, K., Matsumoto, K., Saito, H., Tsumaki, N., Takahashi, Y., Toyama, Y., Umezawa, A.
  • Journal Title: J Cell Biochem 100 Pages: 1240-1254
  • Peer Reviewed
• [Journal Article] Bone morphogenetic proteins in bone stimulate osteoclasts and osteoblasts during bone development. (2006)
  • Author(s): Okamoto, M., Murai, J., Yoshikawa, H., Tsumaki, N.
  • Journal Title: J Bone Miner Res 21(7) Pages: 1022-1033
  • Peer Reviewed
• [Journal Article] Oxygen tension regulates chondrocyte differentiation and function during endochondral ossification. (2006)
  • Author(s): Hirao, M., Tamai, N., Tsumaki, N., Yoshikawa, H., Myoui, A.
  • Journal Title: J Biol Chem 281(41) Pages: 31079-31092
  • Peer Reviewed
• [Presentation] Role of Smad7 during endochondral bone formation. (2007)
  • Author(s): T. Iwai, J. Murai, H. Yoshikawa, N. Tsumaki
  • Organizer: Gordon Research Conference
  • Place of Presentation: Cartilage Biology & Pathology, Ventura, CA USA
  • Year and Date: 20070304-20070309
• [Book] 最新整形外科学体系1運動器の生物学と生体力学(越智隆弘総編中村利孝、吉川秀樹編)骨形成 (2008)
  • Author(s): 越智隆弘, 中村利孝、吉川秀樹
  • Total Pages: 30-37
  • Publisher: 中山書店