Identification of novel protein biomarkers for knee osteoarthritis by integrating human plasma proteome: evidence from Mendelian randomization and preliminary in vitro investigation

Objective: experiments. Methods: exploration was conducted using macrophages (MØs) and synovial fibroblasts (SF) to assess biological plausibility. Results: experiments revealed that galectin-3 stimulation upregulated the expression of inflammatory cytokines (tumor necrosis factor alpha, interleukin-1β, and interleukin-18) and related inflammatory mediators (proteinase 3 [encoded by PRTN3] and myeloperoxidase [encoded by MPO]) in MØs, suggesting a potential pro-inflammatory association. Conclusion: experiments provide preliminary biological plausibility for galectin-3-mediated inflammatory responses, suggesting potential involvement of myeloperoxidase and proteinase 3. These findings offer novel etiological insights and position galectin-3 as a therapeutic target, which warrants further exploration.