Objective      To investigate the effect of transforming growth factor beta type Ⅰ receptor（TGF-βRⅠ） inhibitor SB-505124 on the proliferation

differentiation and extracellular matrix of chondrocytes.       Methods      The expression of p-Smad2/3 in ATDC5 cells that were treated with different concentrations of SB-505124 was analyzed by Western blotting. The effect of SB-505124 on proliferation of ATDC5 cells was detected by MTT assay. The effect of SB-505124 on the expression of c-Myc protein was analyzed by Western blotting. The effect of SB-505124 on the markers of cell differentiation and extracellular matrix

including collagen Ⅱ

aggrecan and ADAMTS5 were analyzed by real-time PCR. The effect of SB-505124 on expression of sulfated proteoglycans was measured by Alcian blue staining.       Results      Western blotting results showed that the treatment with SB-505124 induced a decline of phosphorylated Smad2/3 (p-Smad2/3)

including carboxyl termini and linker region stimulated by TGF-β1 in ATDC5 cells. MTT assay results demonstrated that SB-505124 significantly inhibited ATDC5 cell proliferation in a dose-and time-dependent manner

and the expression of c-Myc protein was also inhibited. Real-time PCR showed that collagen Ⅱ and aggrecan were inhibited by SB-505124

while ADAMTS5 was elevated by SB-505124. Alcian blue staining showed that the staining intensity was reduced in SB-505124 treated cells.       Conclusion      SB-505124 can block endogenous TGF-β signaling pathway to inhibit cell proliferation

cell differentiation and synthesis of extracellular matrix

and to promote the degradation of extracellular matrix.