title: TGF-beta signaling in chondrocytes.
abstract: 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.
authors.affiliation: Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester School of Medicine, Rochester, NY 14642, USA.
authors.forename: Tian-Fang
authors.initials: TF
authors.lastname: Li
authors.forename: Regis J
authors.initials: RJ
authors.lastname: O'Keefe
authors.forename: Di
authors.initials: D
authors.lastname: Chen
mesh_terms: D000818:Animals; D001846:Bone Development; D001847:Bone Diseases / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta