Integrating Articular Cartilage Histopathology with CTX-II and COMP as Synovial Fluid Biomarkers for a Comprehensive Analysis in Osteoarthritis Evaluation

Abstract

Osteoarthritis (OA) is the most common form of chronic joint disease characterized by the loss of cartilage as the primary site of the lesion. Both collagenous and non-collagenous proteins of the extracellular matrix (ECM) are dysregulated by the cellular component damage. Alterations in cartilage composition may manifest through variations in synovial fluid concentrations of C-terminal cross-linked telopeptides of type II collagen (CTX-II) and cartilage oligomeric matrix protein (COMP). This study seeks to decode histological alterations in the cartilage and establish a symbiotic relationship with concentrations of specific ECM proteins within the synovial fluid as potential OA biomarkers. Twenty-five surgically obtained cartilage tissue samples were stained with toluidine blue and analysed using the OARSI grading system under a light microscope both quantitatively and semi-quantitatively. The presence of CTX-II and COMP proteins was measured in the synovial fluid samples using ELISA. The SPSS 28.0 program was used for statistical data analysis. The OARSI score median value was 4.0 (3.0;4.5), attributable to the delamination of the superficial cartilage zone. A greater number of single cells in comparison with cellular clusters was found: 60.00 (45.00;84.00) and 26.00 (22.00;48.00), respectively. Proteoglycan staining was 1.00 (1.00;2.00), attributable to low intensity. A negative correlation between ECM oedema and proteoglycan staining was found (r = −0.445; p = 0.043). The mean levels of CTX-II and COMP in synovial fluid were 1092 pg/mL (SD 537.95) and 1262 ng/mL (SD 339.47), respectively. There was a positive correlation between CTX-II and OA severity (r = 0.305; p = 0.041); the COMP and OA severity correlation was negative (r = −0.286; p = 0.049). The identified positive correlation between OA severity and CTX-II levels in synovial fluid suggests that CTX-II may hold promise as a valuable biomarker for tracking OA progression. This implication opens up possibilities for early detection and targeted interventions in the management of the disease.