Distinct roles of Smad pathways and p38 pathways in cartilage-specific gene expression in synovial fibroblasts
J. Clin. Invest. Hiroaki Seto, et al. 113:718 doi:10.1172/JCI19899 [Go to this article.]

Figure 5
Segregation of downstream signaling pathways of ALK3. (A) Synergistic effect of Smad1 expression on the chondrogenic effects of the ALK3^CA virus. Expression of Smad1 (MOI = 20) together with ALK3^CA virus (MOI = 2) strongly induced expression of type II collagen in SFs. White bars indicate type II collagen expression on day 1 of cultures, and black bars indicate that on day 3. **P < 0.005 (significantly different). (B) MKK6-p38 pathways promote terminal chondrocytic differentiation of SFs. Mandatory activation of p38 pathways by expression of MKK6^CA using adenovirus vectors rapidly activated expression of the Sox9 and type II collagen genes, which rapidly declined, while expression of a terminal chondrocytic differentiation marker, type X collagen, was gradually increased. Adenovirus vector–mediated overexpression of Smad1 together with MKK6^CA suppressed type X collagen expression and maintained type II collagen expression in SFs. *P < 0.001; **P < 0.005 (significantly different).