Proteomic Insights Into Early Detection and Progression of Knee Osteoarthritis: Unveiling Molecular Signatures

Osteoarthritis (OA) is the eleventh most disabling condition, with radiographic classification based on the Kellgren-Lawrence (KL) grading system. Early detection is critical to implement interventions to slow disease progression and improve patient outcomes. Proteomics, as a powerful strategy, could contribute to a better understanding of the disease pathophysiology and its early detection.

The study aims to identify and confirm proteins associated with early detection and their role in the progression of knee OA.

Synovial fluid (SF) and serum samples from the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, were categorized by KL classification and subjected to SWATH^TM analysis in the discovery phase. Seven samples of each OA grade were analyzed. A mass dynamics tool was used for data analysis and visualization. Significant protein expression level was defined as -1≤ log2FC ≥1 with p-value <0.05, and ELISA was used for validation in a greater number of patients.

29 significantly modulated proteins were observed in osteoarthritis grade comparisons. Cathepsin G (CTSG) and angiotensinogen (AGT) were upregulated, whereas fumarylacetoacetase (FAH) and neural cell adhesion molecule 1 (NCAM1) were downregulated with radiographic disease progression, as validated by ELISA. CTSG, AGT, and NCAM1 showed good sensitivity and specificity in discriminating between early and late OA grades. Notably, serum and synovial fluid levels of AGT and NCAM1 exhibited significant correlation.

This is one of the first studies to comprehensively analyze proteins associated with OA progression. Additionally, the identified protein signatures have great potential for OA progression and differential diagnosis of early and late-stage OA.