Procollagen II C-propeptide in joint fluid: Changes in concentration with age, time after knee injury, and osteoarthritis

Objective. To determine in a cross sectional study the concentrations in joint fluid of the C-propeptide of collagen II (pCol II-C) in patients with knee injury and developing osteoarthritis (OA). Methods. Synovial fluid (SF) samples were collected from knees of healthy volunteers, from patients with injury to the knee causing lesions of the anterior cruciate ligament and/or menisci, and from patients with posttraumatic or primary OA. Concentrations of pCol II-C were determined by enzyme immunoassay with a polyclonal antiserum against the bovine propeptide. Results. The median concentration of pCol II-C in joint fluid in the reference group was 1.3 ng/ml (range 0.1-5.7 ng/ml). Median concentrations of pCol II-C in joint fluid were increased 2-4-fold in all 3 study groups over that in the reference group. Very high concentrations of propeptide were noted in samples from patients younger than about 18 years. Propeptide concentrations were increased after knee injury, with a suggested peak at about 1-4 years evident for patients with cruciate ligament injury. pCol II-C levels were increased at all stages of OA development, except in the most advanced phases. Conclusion. The increased levels of pCol II-C in SF may reflect an increased rate of synthesis of collagen II in the joint cartilage of patients with knee injury and developing OA. The increase reaches a maximum well before radiographic changes indicative of OA are apparent, and occurs during a disease phase characterized by signs of increased degradation of collagen II, aggrecan, and other matrix components. Further studies of markers of matrix metabolism of cartilage, bone, and other joint tissues in human and animal models of OA may aid in the identification of process markers, individuals at risk, and new therapeutic targets.