To examine effects of carprofen (enantiomers and a racemic mixture) on the metabolism of equine chondrocytes.
Cartilage from clinically normal horses.
Effects of carprofen on proteoglycan neosynthesis, glycosaminoglycan (GAG) release and prostaglandin (PG) E2 production by unstimulated chondrocyte monolayers and cartilage explants were examined, as were similar variables in monolayers and explants exposed to carprofen and recombinant human interleukin 1beta (IL-1). Carprofen (enantiomers and racemic mixture) was used alone or along with IL-1 on monolayers and explant cultures. Medium was collected 48 to 96 hours later, and cartilage was digested. Proteoglycan synthesis was assessed as the amount of 35S-labeled proteoglycan in medium and digested cartilage. Total GAG content of the medium and digested cartilage was measured, and proteoglycan degradation was calculated. Radioimmunoassay was used to measure PGE2 production.
Carprofen significantly decreased PGE2 production by unstimulated chondrocytes and antagonized an IL-1-induced increase in PGE2 production. Carprofen significantly increased proteoglycan synthesis in unstimulated monolayers and explants. Concurrently, there was a decrease in GAG release by explants. Use of IL-1 significantly decreased proteoglycan synthesis, but the highest concentrations of carprofen partially reversed this effect in chondrocyte monolayers.
Use of carprofen in osteoarthritic horses may induce beneficial changes in articular cartilage matrix.
Carprofen had a potentially beneficial effect on proteoglycan metabolism of equine chondrocytes. This effect was sufficiently strong at the highest concentrations to overcome inhibitory effects of IL-1 on proteoglycan synthesis. Carprofen also inhibited PGE2 production by unstimulated and IL-1-stimulated chondrocytes. Carprofen induced these enantiomer-specific effects.