PP2 Alleviates The Progression Of Osteoarthritis By Inhibiting Wnt/β-Catenin And Activating TGF-β/Smad Signaling

Objective: Explore the effect and mechanism of Src inhibitor PP2 on knee osteoarthritis.Methods: The protein expressions of Src,p-Src(y418)and p-FAK in normal and OA human chondrocytes were detected by immunofluorescence(IF).The chondrocytes of mice were extracted and inoculated into a 6-well plate.The chondrocytes were co-cultured with IL-1 β and different doses of PP2,and then the degeneration of chondrocytes was observed.The OA model was induced by destabilizing medial meniscectomy in the right knee of mice,and then different doses of PP2 were injected intraperitoneally.The samples were taken eight weeks after the operation,and the degree of cartilage degeneration of the knee joint was observed.Results: The levels of Src,p-Src(y418)and p-FAK in knee cartilage tissue of patients with OA were abnormally increased.After chondrocytes were co-treated with IL-1βand different doses of PP2,the results showed that PP2 could reduce the abnormal increase of β-catenin,p-β-catenin and other proteins created by IL-1βand reverse the decrease of p-Smad3,Aggrecan and collagen Ⅱproteins.Meanwhile intraperitoneal injection of PP2 in vivo significantly reduced the degeneration of articular cartilage.Conclusion: Our data show that PP2 can inhibit Wnt/β-catenin and activate TGF-β/ Smad signal pathway,thus protecting the cartilage of OA mice.