Transforming growth factor-beta stimulates cyclin D1 expression through activation of beta-catenin signaling in chondrocytes.
Transforming growth factor-beta (TGF-beta) plays an essential role in chondrocyte maturation. It stimulates chondrocyte proliferation but inhibits chondrocyte differentiation. In this study, we found that TGF-beta rapidly induced beta-catenin protein levels and signaling in murine neonatal sternal primary chondrocytes. TGF-beta-increased beta-catenin induction was reproduced by overexpression of SMAD3 and was absent in Smad3(-/-) chondrocytes treated with TGF-beta. SMAD3 inhibited beta-transducin repeat-containing protein-mediated degradation of beta-catenin and immunoprecipitated with beta-catenin following TGF-beta treatment. Both SMAD3 and beta-catenin co-localized to the nucleus after TGF-beta treatment. Although both TGF-beta and beta-catenin stimulated cyclin D(1) expression in chondrocytes, the effect of TGF-beta was inhibited with beta-catenin gene deletion or SMAD3 loss of function. These results demonstrate that TGF-beta stimulates cyclin D(1) expression at least in part through activation of beta-catenin signaling.
Li
Tian-Fang
TF
Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester, Rochester, New York 14642.
Chen
Di
D
Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester, Rochester, New York 14642.
Wu
Qiuqian
Q
Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester, Rochester, New York 14642.
Chen
Mo
M
Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester, Rochester, New York 14642.
Sheu
Tzong-Jen
TJ
Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester, Rochester, New York 14642.
Schwarz
Edward M
EM
Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester, Rochester, New York 14642.
Drissi
Hicham
H
Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester, Rochester, New York 14642.
Zuscik
Michael
M
Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester, Rochester, New York 14642.
O'Keefe
Regis J
RJ
Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester, Rochester, New York 14642. Electronic address: regis_okeefe@urmc.rochester.edu.
D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation; D019902:Chondrocytes / Q000378:metabolism*; D019938:Cyclin D1 / Q000096:biosynthesis*; D017353:Gene Deletion; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D015293:Transducin / Q000737:chemistry; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D051176:beta Catenin / Q000378:metabolism*
D051900:Smad3 Protein; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D051176:beta Catenin; D019938:Cyclin D1; D015293:Transducin