Proteomic Profiling of Human Synovial Fluid Reveals AKR1C1 as a Biomarker of Osteoarthritis Severity

Pathological changes in the knee joint are reflected in the protein composition of synovial fluid (SF), which is altered in osteoarthritis (OA) and may serve as a source of biomarkers. This study used label-free quantification proteomics to analyze SF protein profiles from individuals with varying grades of cartilage damage and healthy controls. SF samples (n = 61) from healthy knees (grade 0) and OA-affected joints (grades I-IV, Outerbridge score) were analyzed using LC-MS/MS. Feature selection was performed with the Jonckheere-Terpstra nonparametric test. Candidate biomarkers were validated by ELISA in an independent cohort (n = 51), with OA severity graded according to the Kellgren-Lawrence (K/L) scale. Using this approach, nine proteins were significantly differentially expressed between OA and control samples (p < 0.01), showing higher levels in early OA stages compared to moderate and late disease (p < 0.05). Among these, aldo-keto reductase family 1 member C1 (AKR1C1), a protein involved in oxidative stress and autophagy, positively correlated with OA severity in both cohorts. These findings highlight several protein biomarkers with potential utility in early OA diagnosis and monitoring disease progression. Notably, AKR1C1 emerges as a promising diagnostic and prognostic biomarker, warranting further investigation.