Li Tian-Fang, O'Keefe Regis J, Chen Di
Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester School of Medicine, Rochester, NY 14642, USA.
Front Biosci. 2005 Jan 1;10:681-8. doi: 10.2741/1563.
Transforming growth factor-beta (TGF-beta) regulates a large variety of cellular activities. Binding of TGF- beta to its cell surface receptor triggers several signaling cascades, among which the TGF- beta -Smad pathway is the most extensively studied. TGF- beta also activates protein kinases, including MAPK, PKA and PKC, and modulates gene expression via its delicate interaction with other signaling pathways. During endochondral bone formation, TGF- beta acts as a potent inhibitor of the terminal differentiation of epiphyseal growth plate chondrocytes. This effect appears to be primarily mediated by Smad molecules, although MAPK-ATF2 signaling is also involved. The rate of chondrocyte maturation is tightly regulated through the interactions of Smad-mediated signaling, the Wnt signaling pathway, and the transcription factor Runx2. Improving our understanding of the exact mechanisms underlying TGF- beta -mediated signaling pathways and their effects may greatly impact the diagnosis and treatment of many common orthopaedic diseases.
转化生长因子-β（TGF-β）调节多种细胞活动。TGF-β与其细胞表面受体结合会触发多个信号级联反应，其中TGF-β-Smad途径是研究最为广泛的。TGF-β还可激活包括丝裂原活化蛋白激酶（MAPK）、蛋白激酶A（PKA）和蛋白激酶C（PKC）在内的蛋白激酶，并通过与其他信号通路的精细相互作用来调节基因表达。在软骨内骨形成过程中，TGF-β作为骨骺生长板软骨细胞终末分化的强效抑制剂。这种作用似乎主要由Smad分子介导，尽管MAPK-ATF2信号传导也参与其中。软骨细胞成熟速率通过Smad介导的信号传导、Wnt信号通路和转录因子Runx2之间的相互作用受到严格调控。深入了解TGF-β介导的信号通路及其作用的精确机制，可能会对许多常见骨科疾病的诊断和治疗产生重大影响。
