In vivo effects of interleukin-1 on articular cartilage. Prolongation of proteoglycan metabolic disturbances in old mice

Abstract

We investigated the effects of intraarticular injections of interleukin-1 alpha (IL-1 alpha) into the knee joints of young (3-month-old) and old (18-month-old) C57Bl/10 mice. In this in vivo study, 35S-sulfate incorporation and release were used to compare the effects of IL-1 on patellar cartilage proteoglycan metabolism. IL-1-induced stimulation of proteoglycan degradation was confined to the first 24 hours after injection in both young and old animals, and was only slightly lower in old cartilage than in young. In old patellar cartilage, IL-1-induced suppression of proteoglycan synthesis appeared to be more prolonged. Also, the amount of time needed to restore the cartilage matrix, characterized by proteoglycan synthesis above normal levels, was longer in old animals. Histologic analysis confirmed the retarded recovery in the cartilage of old mice. Autoradiography showed that the chondrocytes of the medial side of the femorotibial area were most vulnerable to IL-1-induced suppression of proteoglycan synthesis, especially the medial tibial plateau. As with the patellar cartilage, IL-1-induced suppression of proteoglycan synthesis in this area of articular cartilage was more prolonged in old animals. Our data indicated that the impact of IL-1 on articular cartilage is higher in old mice and that, consistent with certain loci found to be at risk in experimental osteoarthritis, there are sites at which IL-1 is more likely to act.