MONO-IODOACETATE-INDUCED EXPERIMENTAL OSTEOARTHRITIS - A DOSE-RESPONSE STUDY OF LOSS OF MOBILITY, MORPHOLOGY, AND BIOCHEMISTRY

Objective, To characterize the dose-responsiveness of morphologic and biochemical chondral changes relative to mobility in mono-iodoacetate (MIA)-induced osteoarthritis (OA) in rats, Methods. Rat mobility was a ssessed by biotelemetry. Articular lesions mere characterized by macro scopic and histologic examinations. Cartilage proteoglycan metabolism was evaluated by the 1,9-dimethglmethylene blue dye binding assay and by radiosulfate incorporation in patellar cartilage, Results. Spontane ous locomotor activity was rapidly, transiently, and dose-dependently decreased after MIA injection into rat knees (primary response), There after, only high doses (0.3 mg and 3.0 mg) led to a secondary progress ive long-term loss of spontaneous mobility on day 15, when subchondral bone vvas exposed, These 2 doses resulted in significant changes in c artilage proteoglycan concentration at day 15 and a strong inhibition of anabolism in the peripheral patellae by day 2, contrasting with the effects of lower doses (0.01, 0.03, and 0.1 mg), Conclusion. When a s ufficient dose of MIA is used, this model can easily and quickly repro duce OA-like lesions and functional impairment in rats, similar to tha t observed in human disease, These parameters, as well as proteoglycan metabolism, could serve as indicators for studying chondroprotective drugs, or for evaluating the ability of imaging techniques to detect a nd evaluate chondral lesions.