Knockdown of postn attenuates osteoarthritis via TGF-β/smad signalling pathway

Purpose: To examine the role of Postn and its underlying mechanisms in cartilage during OA development. Methods: Postn expression in osteoarthritic cartilage from humans and mice was analyzed by qPCR, western blot and immunohistochemistry. In vitro and in vivo studies were performed y knocking down Postn using siRNA and lentivirus in ATDC5 cells and C57/BL6 mice respectively. Western blot, qPCR, histology and immunohistochemistry were used to assess Postn function and TGF-β/SMAD signalling pathway. Results: Postn was up-regulated in osteoarthritic cartilage from humans and mice, and increased as OA progressed. Knockdown of Postn by siRNA in ATDC5 cells down-regulated Mmp13, Col10a1, Runx2 and Vegf, accompanied by up-regulated Col2 after treatment of IL-1β. Intra-articular injection of lentivirus-shPostn led to attenuation of osteoarthritis in mice after DMM surgery. Knockdown of Postn reduced TGF-β induced Col X and Mmp13 expression. Postn activation in response to TGF-β1 was dose- and time-dependent and caused cartilage degeneration via TGF-β/SMAD signalling pathway. Conclusions: Our findings demonstrated that Postn was over-expressed in osteoarthritic cartilage and accelerated cartilage degeneration via TGF-β/SMAD signalling pathway. These results suggest that Postn is a potential therapeutic target for OA.