The Influence of Temperature and Fibril Stability on Degradation of Cartilage Collagen by Rheumatoid Synovial Collagenase

Crude synovial collagenase, an enzyme that may affect joint cartilage in rheumatoid arthritis, can destroy whole articular cartilage. To study this phenomenon under more specific conditions, we purified collagenase synthesized by primary cultures of rheumatoid synovium and used it to degrade collagen fibrils purified from human articular cartilage. These highly cross-linked fibrils were resistant to solubilization in acetic acid-pepsin extracts and, in comparison with skin collagen fibrils reconstituted without intermolecular cross-links, were somewhat resistant to the collagenase as well. However, the rate of cartilage collagen lysis was affected by changes in reaction temperature. At temperatures found within rheumatoid knee joints (36°C) collagenolysis was four times greater than at temperatures found in normal knee joints (33°C). Part of the benefit from anti-inflammatory therapy in rheumatoid arthritis may be secondary to decreasing intra-articular temperatures, thereby decreasing the rate at which collagenase degrades cartilage collagen. (N Engl J Med 290: 1–6, 1974)