In vitro stimulation of equine articular cartilage proteoglycan synthesis by hyaluronan and carprofen

Abstract

The effects of hyaluronan and carprofen (both racemic mixture and separate R and S enantiomers) on proteoglycan (PG) synthesis by equine cultured chondrocytes and cartilage explants were examined. Hyaluronan stimulated PG synthesis in both cell and explant cultures. The concentration-response curve of the latter was bell-shaped. Racemic carprofen and R and S enantiomers also stimulated PG synthesis, although concentration-response relationships varied for each preparation and high concentrations inhibited synthesis. It was concluded that (a) hyaluronan exerts a stimulatory effect on PG synthesis at low concentrations and (b) stimulatory effects of carprofen on PG synthesis are, to some degree, enantioselective with the carprofen S-enantiomer exerting the greatest effect. Hyaluronan and carprofen are used clinically despite incompletely understood mechanisms of action. These results suggest (a) hyaluronan and carprofen might exert an anti-arthritic action through stimulation of PG synthesis and (b) there is possible justification for therapeutic administration of enantiomeric rather than racemic carprofen.