Usefulness of specific OA biomarkers, thrombin-cleaved osteopontin, in the posterior cruciate ligament OA rabbit model

Abstract

We undertook this study to determine whether thrombin-cleaved osteopontin (OPN) in synovial fluid (SF) represents a useful marker of osteoarthritis (OA) progression in the posterior cruciate ligament transection (PCLT) OA rabbit model. PCLT was performed on the right knee joints of 48 rabbits. The rabbits were then sacrificed separately at 4, 8, 16, and 24 weeks post-surgery, when the joint was harvested and macroscopic and histological assessments of articular cartilage were performed. Thrombin-cleaved OPN product in SF was determined using Western blotting and the levels were measured using an enzyme-linked immunoassay. The macroscopic and histological scores for PCLT knees were already elevated 4 weeks after surgery and increased with time. Western blotting showed the presence of thrombin-cleaved OPN in SF from PCLT knees. Thrombin-cleaved OPN levels in SF were elevated at 4 weeks (P < 0.001) and were elevated peaking at 24 weeks (P < 0.00001) after PCLT compared to baseline. A positive significant correlation was found between thrombin-cleaved OPN levels and the macroscopic scores (8 weeks: ρ = 0.695, P = 0.012; 16 weeks: ρ = 0.751, P = 0.005; 24 weeks: ρ = 0.660, P = 0.020). Furthermore, the same correlation was noted between thrombin-cleaved OPN levels and the histological scores (4 weeks: ρ = 0.609, P = 0.036; 8 weeks: ρ = 0.662, P = 0.019; 16 weeks: ρ = 0.827, P = 0.001; 24 weeks: ρ = 0.813, P = 0.001). In this rabbit model of PCLT, thrombin-cleaved OPN levels in SF appear to provide a useful marker of OA disease severity and progression.