EFFECT OF CARPROFEN ON SULFATED GLYCOSAMINOGLYCAN METABOLISM, PROTEIN-SYNTHESIS, AND PROSTAGLANDIN RELEASE BY CULTURED OSTEOARTHRITIC CANINE CHONDROCYTES

Objective-To determine whether the nonsteroidal anti-inflammatory drug carprofen directly influences canine chondrocyte metabolism. Animals- Cartilage from the femoral heads of 73 dogs undergoing total hip repla cement. Procedure-Rates of glycosaminoglycan (GAG) synthesis and degra dation, protein synthesis, cell viability, and prostaglandin release w ere determined in canine explant cartilage or monolayer canine chondro cyte cultures in the presence of 0 to 100 mu g of carprofen/ml. Rate o f GAG synthesis was assessed as incorporation of [S-35]sulfate into ca rtilage matrix during a 3-hour pulse label. Degradation of cartilage G AG was assessed as rate of release of [S-35]sulfate from prelabeled ex plant cultures. Rates of total protein synthesis were assessed as inco rporation of [S-35]methionine into trichloracetic acid precipitable ma terial during a 3-hour pulse label. Radiolabeled chondrocyte proteins were separated by polyacrylamide gel electrophoresis and visualized by fluorography. Rates of prostaglandin E(2) release were assessed by ra dioimmunoassay. Results-Carprofen stimulated a significant increase in the rate of GAG synthesis at concentrations of 1 and 10 mu g/ml, with no change in total protein synthesis, pattern of new protein synthesi s, or cell viability. At concentration greater than or equal to 20 mu g/ml, inhibition of GAG synthesis and total protein synthesis was obse rved. There was no significant change in rate of release of GAG from c artilage explants, but potent inhibition of prostaglandin release was observed. Conclusions-Carprofen has a direct influence on chondrocyte activity, resulting in changes in rate of production of cartilage matr ix. Clinical Relevance-In determining the optimal therapeutic dose of carprofen for arthritic conditions in dogs, it is important to conside r potential influences on cartilage, as well as anti-inflammatory acti ons.