Osteoprotegerin is induced by transforming growth factor-beta 1 and regulates pro-fibrotic responses in human dermal fibroblasts.

Transforming growth factor-beta1 (TGF-β1) is known to play a key role in the progression of organ fibrosis. Here, we demonstrate that TGF-β1 induces osteoprotegerin (OPG) expression in human dermal fibroblasts (HDFs) at both protein and mRNA levels. OPG neutralization has led to attenuation of TGF-β1-mediated profibrotic effects in HDFs. Further, we found that recombinant OPG induced fibronectin (FN) production and alpha-smooth muscle actin (α-SMA) expression. Interestingly, the OPG-mediated effect was significantly attenuated by αvβ3-integrin inhibitors (cyclo(RGDfK) and cilengitide) suggesting that OPG exerts profibrotic responses in human dermal fibroblasts by regulating αvβ3-integrin activation. Taken together, our data suggest that OPG expression is stimulated by TGF-β1 and contributes to dermal fibroblast activation.