Denaturation of type II collagen in articular cartilage in experimental murine arthritis. Evidence for collagen degradation in both reversible and irreversible cartilage damage

Degradation of type II collagen is thought to be a key step in the destruct ion of articular cartilage in patients with rheumatoid arthritis or osteoar thritis. The aim of this study was to investigate whether type II collagen degradation is associated with cartilage destruction. Type II collagen degr adation was studied in two murine arthritis models, zymosan-induced arthrit is (ZIA), which develops reversible articular cartilage damage based on pro teoglycan analysis, and antigen-induced arthritis (AIA), in which there is irreversible damage to the cartilage. Type II collagen degradation was assa yed immunohistochemically using the COL2-3/4m antibody which recognizes den atured type II collagen, such as is produced by collagenase cleavage. ID bo th models, degradation of type II collagen was observed in the nan-calcifie d articular cartilage of arthritic but not of control knees. In the patella -femoral compartment, collagen denaturation started to increase on day 3 (Z IA) and day 7 (AIA) and remained high on day 14. In contrast, in the tibia- femoral compartment, type II collagen breakdown was not increased before 14 days in either model. By 28 days, collagen denaturation was strongly reduc ed in the patella-femoral compartment in the ZIA model, but persisted in th e tibia-femoral compartment in both models. In conclusion, increased type I I collagen degradation was found in articular cartilage of both ZIA and AIA animals. Since ZIA does not develop irreversible cartilage destruction, th is indicates that cartilage may have the ability to withstand a limited deg ree of type II collagen degradation without developing irreversible damage. (C) 1999 John Wiley & Sons, Ltd.