Rac1 signaling regulates CTGF/CCN2 gene expression via TGFβ/Smad signaling in chondrocytes

SummaryObjectiveConnective tissue growth factor (CTGF) has been implicated in regulation of chondrocyte differentiation at multiple steps and has been implicated in the progression of diseases such as scleroderma and osteoarthritis. However, the pathways mediating the expression of CTGF/CCN2 and related factors in cartilage are not fully understood. We have previously shown that the Rho family of proteins and the actin cytoskeleton regulate both early and late chondrocyte differentiation.ResultsHere we demonstrate that several CTGF/Cyr61/Nov (CCN) family members are differentially affected by either inhibition of actin polymerization (cytochalasin D treatment), promotion of actin polymerization (jasplakinolide treatment), inhibition of RhoA/rho kinase (ROCK) signaling (Y27632 treatment) and Rac1 signaling. We also show that the Smad site in the CTGF/CCN2 promoter is responsive to both Rac1 inhibition and cytochalasin D treatment, suggesting a role of TGFβ/Smad signaling in mediating the effects of actin dynamics and Rac1.ConclusionCollectively, these data show that Rac1 and actin pathways control CTGF/CCN2 expression in chondrocytes which might be relevant to both skeletal development and associated diseases such as osteoarthritis.