Exploring potential therapeutic targets for osteoarthritis using proteomics combined with Mendelian randomization

Background Osteoarthritis (OA) is a common chronic degenerative joint disease. Currently, treatments for the mechanisms underlying OA are lacking. Therefore, his study explored potential therapeutic targets for OA using proteomic and Mendelian randomization (MR) analyses. Methods The knee cartilage of patients with knee osteoarthritis (KOA) and tibial plateau fractures served as the experimental and control groups, respectively. The correlation between the platelet degranulation signaling pathway and KOA pathogenesis was determined using proteomics analysis. We performed a two-sample MR analysis to compare the effects of clopidogrel and aspirin on KOA onset. The literature search results suggested that the ADAMTS family of metalloproteinases is associated with platelet degranulation signaling pathways; therefore, we conducted MR analyses of drug targets to further explore potential therapeutic targets for KOA and extend the screening results to hip osteoarthritis (HOA). Results Proteomics analysis indicated that the platelet degranulation signaling pathway is involved in the pathogenesis of KOA. Following the MR analysis, ADAMTS-1, ADAMTS-5, and ADAMTS-13 were identified as potential targets for OA therapy. Only ADAMTS-13 expression was significantly associated with HOA onset. Conclusion This study provides novel insights into developing targeted treatments for OA, which could significantly improve patient outcomes and quality of life.