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 ost eoarthritic (OA) cartilage continue to show increased synthesis and tu rnover of proteoglycans (PGs) during explant culture. A comparison was also made between the responsiveness of experimental OA and control c artilage to interleukin-1 beta (IL-1 beta) and tumor necrosis factor a lpha (TNF alpha) after 1 day and 3 days in culture. Methods. OA was in duced in mature animals by sectioning of the anterior cruciate ligamen t followed by 3 months of normal exercise, PG synthesis in the articul ar cartilage was determined by measuring S-35-sulfate incorporation du ring explant culture over 1-3 days. Inhibition of PG synthesis was als o determined with various concentrations of IL-1 beta and TNF alpha af ter 1 and 3 days in culture. PGs extracted from the articular cartilag e over 1-3 days in culture were examined by agarose-polyacrylamide gel electrophoresis, Results, Up to 24 hours after excision from the join t, PG synthesis was higher in experimental OA cartilage than in contro l cartilage. It was also less sensitive to inhibition by TNF alpha. Th ese differences were no longer detected after 48-72 hours in culture, There were no changes in the relative proportions of aggrecan and deco rin/biglycan extracted from and synthesized by control and experimenta l OA cartilage over the 3 days in culture. Conclusion, Previous result s indicated that PG synthesis and turnover in articular cartilage was increased for many months after induction of experimental OA. Our pres ent results show that the enhanced rate of PG synthesis and turnover w ere evident in freshly explanted tissue, but the differences were lost over 3 days in culture, A decreased responsiveness to TNF alpha was a lso lost, The hypermetabolic activity of experimental OA chondrocytes was thus reversible and not a permanent change in chondrocyte phenotyp e.