Analysis of the role of TGF-b family and Smad signaling in musculoskeletal regulation

2014 Fiscal Year Final Research Report

• Project/Area Number: 24592278
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Saitama Medical University
• Principal Investigator: YONEYAMA Katsumi 埼玉医科大学, 医学部, 助手 (20571574)
• Co-Investigator(Kenkyū-buntansha): KATAGIRI Takenobu 埼玉医科大学, 医学部, 教授 (80245802)
• Co-Investigator(Renkei-kenkyūsha): OHTE Satoshi 埼玉医科大学, 医学部, 助教 (00547979) ; SASANUMA Hiroki 埼玉医科大学, 医学部, 研究員 (30571707) ; MIYAMOTO Arei 埼玉医科大学, 医学部, 研究員 (70634591) ; OSAWA Kenji 埼玉医科大学, 医学部, 助教 (70638238)
• Research Collaborator: TSUKAMOTO Sho 埼玉医科大学, 医学部 (20707658)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 転写因子 / 細胞内伝達情報 / 分化 / 骨格筋 / 運動器

Outline of Final Research Achievements

Transforming Growth Factor-β (TGF-β) family cytokines play crucial role for musculoskeletal development, regeneration and homeostasis. To clarify the molecular mechanisms of TGF-β family, we developed a mouse line carrying skeletal muscle-specific knockout of Smad4, which is an essential transcriptional factor for intracellular signaling of TGF-β family. Because the muscle-specific Smad4 KO mice were lethal, we prepared mononuclear cells from the skeletal muscle tissue of the Smad4 floxed mice and cultured them in vitro. A deletion of Smad4 in the cells by expression of Cre DNA recombinase in vitro stimulated differentiation into myocytes and myotubes, suggesting that Smad4 represses myogenesis in myoblasts. These findings suggest that the Smad4-dependent intracellular signaling of the TGF-β family plays an important role during skeletal muscle development. These findings may provide new therapeutic strategies for diseases caused by dysregulation of the TGF-β family signaling.

Free Research Field

医歯薬学