Bovine Chronic Osteoarthritis Causes Minimal Change in Synovial Fluid

Abstract

Chronic osteoarthritis (OA) is a degenerative disease of the articular cartilage. DNA-binding high mobility group protein B1 (HMGB1) is released on cellular death/activation and acts as an endogenous danger signal and a proinflammatory cytokine. Matrix metalloproteinase (MMP)-2 and in MMP-9 are induced to mediate proteolytic degradation/remodelling of joint tissues. Collagen degradation in the bone and synovium leads to release of type I collagen-derived cross-linked carboxy-terminal telopeptide (ICTP). These molecules have been linked to the pathogenesis of OA and could have potential as synovial fluid (SF) biomarkers in OA. Cartilage and SF were obtained from 27 dairy bulls (30-61 months old) and control cartilage from six young healthy dairy bulls. OA lesions were evaluated grossly (five grades), histologically (seven Osteoarthritis Research Society International [ORSI] grades) and immunohistochemically (four HMGB1 grades). The OARSI lesion score was calculated as the product of the OARSI grade and the OARSI score (the total area of the lesions). SF concentrations of HMGB1, MMP-2 and -9 and ICTP were measured by enzyme-linked immunosorbent assay, gelatin zymography and radioimmunoassay, respectively. Seventy-two percent (39/54) of stifle joints and 85% (23/27) of the dairy bulls had at least one gross OA lesion and 94% of the lesions were localized to the distal end of the femur, with the patellar groove and the lateral trochlear ridge being predilection sites. Gross and histological grades correlated with the HMGB1 grade, but SF total cell count, percent neutrophils or the measured biomarkers did not correlate with the tissue lesions, with the exception of ICTP concentration, which correlated with the total joint score. The switch of HMGB1 from DNA-binding nuclear protein to an extracellular alarmin/cytokine correlates with the gross and histological grades of OA tissue lesions. However, the activity and extent of the tissue lesions did not correlate with other SF biomarkers, perhaps because the histological grades represent outcome measures, while SF reflects process parameters. The only exception was ICTP concentration, which reflects enhanced destruction/remodelling.