Rapid induction of early osteoarthritic-like lesions in the rabbit knee by continuous intra-articular infusion of mammalian collagenase or interleukin-1

Abstract
Aminophenyl mercuric acetate (APMA)-activated collagenase (C) (60 U/ml) obtained fromin vitro cultures of human skin fibroblasts or recombinant interleukin-1β (IL-1β) (200 U/ml) was infused continuously for 7 days into the rabbit knee synovial space by means of an implanted Alzet osmotic pump. In stability studiesin vitro, activated C or IL-1 incubated for 7 days at 37°C, showed no significant loss of biological activity. Alterations in knee cartilage morphology and proteoglycan (PG) content were determined histologically, and the incidence of cartilage damage calculated. C or IL-1 vehicles infused for 7 days, caused on damage. Incidences of damage for C or IL-1 (n=8–9), respectively, were as follows: loss PG: 88% and 100%; chondrocyte disorganiation and loss, 50% and 78%, fissures and or fraying, 25% and 78%; and convergence of inflammatory cells, 25% and 66%. These results confirm the important role of C and IL-1 in cartilage damage.