Longitudinal characterization of synovial fluid biomarkers in the canine meniscectomy model of osteoarthritis

Damage to the meniscus can lead to posttraumatic osteoarthritis. Early mark ers of joint injury and tissue disease may be useful in developing and admi nistering clinical treatment. We investigated the effects of total medial m eniscectomy on biomarkers measured serially in synovial lavage fluid each m onth for 3 months. Following meniscectomy in dogs, four biomarkers were eva luated: cartilage oligomeric matrix protein, keratan sulfate epitope (5D4), the 3B3(-) neoepitope of chondroitin-6-sulfate, and the 3B3(+) chondroitin ase-generated epitope of chondroitin-6-sulfate. Meniscectomy led to statist ically significant elevations of all four biomarkers, with levels peaking a t 4 weeks. By 12 weeks, the level of the 5D4 epitope returned to the preope rative baseline level whereas that of cartilage oligomeric matrix protein, 3B3(-), and 3B3(+) remained above the baseline. Concentrations of these bio markers in the knees not operated on did not change significantly from the baseline. The levels of cartilage oligomeric matrix protein and 3B3(-) rela tive to 3B3(+) remained constant in all knees. In contrast, the level of 5D 4 relative to 3B3(+) declined over time in the knee operated on but remaine d constant in the knee not operated on. These results demonstrate a quantit ative change in the molecular components of synovial fluid after meniscecto my, as well as a qualitative change evinced by an alteration in the relativ e proportions of these epitopes. Extensive analyses showed a strong correla tion between serum levels of 3B3(-) from the femoral and cephalic veins; ho wever, serum 3B3(-) was not correlated with synovial fluid 3B3(-). These fi ndings support the hypothesis that the concentrations of select cartilage b iomarkers in synovial fluid are altered following meniscectomy and are prom ising tools for objectively monitoring the induction of osteoarthritis in t his model system.