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. Author manuscript; available in PMC: 2013 Oct 1.
Published in final edited form as: Arthritis Rheum. 2012 Oct;64(10):3278–3289. doi: 10.1002/art.34566

Figure 6. Proposed schematic of TGF-β signaling in articular cartilage.

Figure 6

TGF-β regulation of MMP-13 in articular chondrocytes is dynamic. In vitro, the early response is dominated by Smad3-repression of MMP-13 while the response at later time points is dominated by p38-mediated induction of MMP-13. The mechanisms may involve modulation of lineage-specific transcription factors Sox9 and Runx2, which form transcriptional complexes with CBP and HDACs, as previously reported in chondrocytes (37) and osteoblasts (38). Thus, loss of Smad3 in vivo results in cartilage degradation due to a reduction in Col2 synthesis and an increase in MMP-13-mediated degradation.