PROTEOGLYCAN LOSS AND SUBSEQUENT REPLENISHMENT IN ARTICULAR-CARTILAGEAFTER A MILD ARTHRITIC INSULT BY IL-1 IN MICE - IMPAIRED PROTEOGLYCANTURNOVER IN THE RECOVERY PHASE

The reparative responses of articular cartilage after an arthritic ins ult have not been studied extensively to this day. In the present stud y, we injected interleukin-l (IL-1) into knee joints of mice to provok e a mild and transient arthritic insult, and characterized both the ca tabolic and the subsequent recovery phase. In the catabolic phase, whi ch lasted 2 days after IL-1 injection, proteoglycan (PG) breakdown was profoundly accelerated and PG synthesis was markedly inhibited. Sulfa tion and polysaccharide synthesis were not affected, yet the number of chondroitin sulfate chains was decreased. The general chondrocyte pro tein synthesis was not inhibited by IL-1. IL-1 injected every other da y for a total of three injections prolonged this catabolic phase and r esulted in frank loss of articular cartilage proteoglycans. In the rec overy phase, started 3 days after IL-1, PG synthesis was enhanced (1.7 times the normal) and proteoglycans had normal hydrodynamic propertie s. Remarkably, PG degradation was significantly decreased (approximate ly 50% of the normal). Zymographic analysis demonstrated enhanced expr ession of gelatinolytic activities in the extracts of the articular ti ssues shortly after IL-1 exposure and decreased levels in the recovery phase. We found that the overshoot of PG synthesis and impaired degra dation act together to facilitate full cartilage repair 7 days after t he last of the three IL-1 injections.