EFFECT OF INTERLEUKIN-1 ON ARTICULAR-CARTILAGE FROM YOUNG AND AGED HORSES AND COMPARISON WITH METABOLISM OF OSTEOARTHRITIC CARTILAGE

The effect of interleukin 1 (IL-1) on equine articular cartilage was i nvestigated, using a cartilage explant culture system. Measurement of ([S]O4)-S-34 incorporation revealed synthesis of matrix proteoglycan b y cartilage to be decreased 45, 59.7, and 37.5% after 1, 3, and 5 days , respectively, in culture in the presence of 5 U of IL-1/ml. There wa s no change in proteoglycan degradation as determined by measurement o f ([S]O4)-S-34 release into the culture medium. Sodium dodecyl sulfate -polyacrylamide gel electrophoresis of cartilage-conditioned medium in dicated that exposure of cartilage to IL-1 caused a decrease in total protein synthesis by 45, 68, and 87% after 1, 3, and 5 days, respectiv ely, in culture while selectively inducing synthesis of the 57-kd neut ral metalloproteinase stromelysin (matrix metalloproteinase-3) in youn g and adult horses. Identification of stromelysin was confirmed by fun ctional characterization and immunoprecipitation. Baseline total prote in synthesis, as well as specific synthesis of stromelysin in cartilag e from adult and aged horses, was markedly less than that of young hor ses. The IL-1-induced reduction in total protein synthesis may not be a characteristic of equine articular cartilage from affected joints of horses with naturally acquired osteoarthritis as indicated by an over all increase in protein synthesis by osteoarthritic explants. Introduc tion of IL-1 into an equine articular cartilage explant culture system resulted in decrease of matrix component synthesis and increase in sp ecific degradative enzyme synthesis and activity. Articular cartilage from aged horses had markedly less overall metabolic activity, compare d with cartilage from young horses. Articular cartilage from affected joints of horses with naturally acquired osteoarthritis did not have m etabolic alterations identical to those of IL-1-stimulated normal arti cular cartilage from the same individual, necessitating reevaluation o f the validity of the IL-1-induced model of osteoarthritis. Osteoarthr itis is a common, naturally acquired disease of horses, and tissue fro m animals of all ages and stages of osteoarthritis is available. The e quine model of osteoarthritis may afford an important means of studyin g the alterations in articular cartilage metabolism as a function of a ge and disease severity.