Moderation of iodoacetate-induced experimental osteoarthritis in rats by matrix metalloproteinase inhibitors

Objective: To determine the effect of matrix metalloproteinase (MMP) inhibi tors in mono-iodoacetate-induced arthritis in rats. Design: The ability of compounds to inhibit MMPs in vitro was assessed kine tically using a quenched fluorescent substrate. Rats were injected with iod oacetate intraarticularly in one knee joint and damage to the tibial platea u was evaluated from digitized images captured using an image analyser and by histology. Collagenase and gelatinase activity in cartilage from iodoace tate injected knees were evaluated using H-3-rat type I collagen and gelati n zymography, respectively. Results: Collagenase and gelatinase activity significantly increased in the knee cartilage of rats injected with iodoacetate with peak activity by day 7. Three MMP inhibitors were examined for their efficacy in the rat iodoac etate-induced arthritis model. Significant (P<0.05) inhibition of cartilage damage was observed in animals treated orally with 35 mg/kg b.i.d. of the three different MMP inhibitors. Inhibition of cartilage damage by the MMP i nhibitors ranged from 36-42%. Conclusion: MMP inhibitors are partially protective against cartilage and s ubchondral bone damage induced by iodoacetate. These results support an imp ortant role for MMPs in mediating the joint damage in this model of arthrit is. (C) 2001 OsteoArthritis Research Society International.