Synovial fluid levels of bradykinin correlate with biochemical markers for cartilage degradation and inflammation in knee osteoarthritis

Objective: To determine the content of bradykinin (BK) and markers of cartilage degradation and inflammation in the synovial fluid (SF) of patients with knee osteoarthritis (OA), and to evaluate correlations with biomarkers or clinical parameters. Methods: SFs were obtained from 30 patients with knee OA. Levels of basal and generated BK, cartilage oligomeric matrix protein (COMP), interleukin (IL) 1, IL-6, IL-8 and matrix metalloprotease (MMP) 1, MMP-3, MMP-13 and sulfated glycosaminoglycans (GAGs) were measured by enzyme-linked immunosorbent assay (ELISA) or colorimetric assays. Results: The mean concentration of basal BK (in the presence of peptidase and protease inhibitors to avoid degradation and de novo formation of BK) was 422pg/ml (95% confidence interval, CI, 281-563) whereas that of invitro generated BK (in the presence of peptidase inhibitors SFs were incubated 60min at 37°C to measure the potential capability to generate BK) was 3427pg/ml (2591-4264). The content of MMP-13, IL-1α, and IL-1β was under assay sensitivity. Basal BK levels positively correlated (Spearman's rank correlation) with GAGs (40μg/ml, 26-54, r=0.4834, P=0.0308) and IL-6 (553pg/ml, 171-935, r=0.3946, P=0.0377) similarly to the generated BK (GAGs, r=0.4563, P=0.0431; IL-6, r=0.5605, P=0.0019). Statistical analysis of basal BK and biomarkers was significant (P=0.0483). When applying a stepwise logistic regression analysis considering biomarkers together with clinical parameters, results indicated that K/L radiographic OA grade and COMP improved the model (P=0.0032). Conclusion: The presence of BK in the knee OA SF and its correlations with cartilage degradation and inflammation markers of OA support its participation in OA pathology.