Intra-articular injection of collagenase induces experimental osteoarthritis in mature rabbits

Objective: The induction of osteoarthritis-like changes by intra-articular injections of collagenase in the knee joint of mature rabbits was examined. Methods: Collagenase (0.5, 1.0 or 2.0 mg) was intra-articularly injected twice into the right knee, and the cartilage and synovia was histologically examined at 6 weeks after the initiation of collagenase injections. In addition, 1 mg of collagenase was intra-articularly injected twice into rabbits, and histological examinations of the cartilage and synovia were performed at various time points. In other experiments, articular cartilage was digested in 5 mi of 0.4 mg/ml collagenase in vitro, and biochemical analyses of the cartilage were performed. Results: The degeneration of the cartilage and synovia were found to be dependent on the dose of collagenase. The cartilage degeneration of the femoral condyle and tibial plateau was more severe at the lateral side than at the medial side. The degeneration of the cartilage progressed, whereas the degeneration of the synovia lessened with time. In the biochemical analyses of the digested cartilage in vitro, the proportion of water increased, and the dry weight of the collected cartilage, the amounts of hydroxyproline and sulfated glycosaminoglycan decreased with the digesting time. Conclusion: These results suggest that collagenase injected intra-articularly digests cartilage directly and stimulates an inflammatory reaction of joint tissues at an early stage, and then cartilage degeneration proceeds. This experimental osteoarthritis is a useful animal model, since the cartilage degeneration is similar to the corresponding lesion in human osteoarthritis, and it is conveniently induced by a dose of collagenase lower than that of papain used, within a short period.