Platelet-rich plasma treatment alleviates osteoarthritis-related pain, inflammation, and apoptosis by upregulating the expression levels of microRNA-375 and microRNA-337

The present study was designed to determine the molecular mechanism by which platelet-rich plasma (PRP) acts on Osteoarthritis (OA) -related pain, inflammation, and apoptosis in vivo and in vitro.An in vivo OA model was established in rats using anterior cruciate ligament transection, and an in vitro OA model was created by treating chondrocytes with IL-1β. Then, the induced rats and chondrocytes were treated with PRP. Real-time PCR were used to examine the expression of micorRNAs (miRs) and mRNAs of inflammatory cytokines. WB were performed to detect the expression of apoptotic factors and Wnt/β-catenin signals. Structural damage of the cartilage and pain in OA rats were analyzed and represented by Mankin Score, OARSIS score, Tender threshold, and Thermal pain threshold. CCK-8 assay and flow cytometry were used to determine cell viability and apoptosis.The expression levels of miR-337 and miR-375 were downregulated in the in vivo and vitro OA models; however, PRP treatment elevated their levels. miR-337 and miR-375 inhibition reversed the effects of PRP of reducing tenderness and thermal pain thresholds in OA rats. Moreover, PRP decreased the mRNA expression levels of MMP-13, Bax, and inflammatory factors, such as IL-1β, IL-18, and TNF-α, as well as increased the expression levels of collagen II and antiapoptotic Bcl-2. The decrease in inflammation and apoptosis was reversed by miR-337 and miR-375 inhibition, respectively.In conclusion, miR-337 and miR-375 are involved in PRP-delayed OA progression by affecting inflammation and apoptosis.