INCREASED PROTEOGLYCAN SYNTHESIS IN CARTILAGE IN EXPERIMENTAL CANINE OSTEOARTHRITIS DOES NOT REFLECT A PERMANENT CHANGE IN CHONDROCYTE PHENOTYPE

Objective, To determine whether chondrocytes in early experimental osteoarthritic (OA) cartilage continue to show increased synthesis and turnover of proteoglycans (PGs) during explant culture. A comparison was also made between the responsiveness of experimental OA and control cartilage to interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) after 1 day and 3 days in culture. Methods. OA was induced in mature animals by sectioning of the anterior cruciate ligament followed by 3 months of normal exercise, PG synthesis in the articular cartilage was determined by measuring S-35-sulfate incorporation during explant culture over 1-3 days. Inhibition of PG synthesis was also determined with various concentrations of IL-1 beta and TNF alpha after 1 and 3 days in culture. PGs extracted from the articular cartilage over 1-3 days in culture were examined by agarose-polyacrylamide gel electrophoresis, Results, Up to 24 hours after excision from the joint, PG synthesis was higher in experimental OA cartilage than in control cartilage. It was also less sensitive to inhibition by TNF alpha. These differences were no longer detected after 48-72 hours in culture, There were no changes in the relative proportions of aggrecan and decorin/biglycan extracted from and synthesized by control and experimental OA cartilage over the 3 days in culture. Conclusion, Previous results indicated that PG synthesis and turnover in articular cartilage was increased for many months after induction of experimental OA. Our present results show that the enhanced rate of PG synthesis and turnover were evident in freshly explanted tissue, but the differences were lost over 3 days in culture, A decreased responsiveness to TNF alpha was also lost, The hypermetabolic activity of experimental OA chondrocytes was thus reversible and not a permanent change in chondrocyte phenotype.