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.