In vitro stimulation of equine articular cartilage proteoglycan synthesis by hyaluronan and carprofen.
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.
Frean
S P
SP
Department of Veterinary Basic Sciences, Royal Veterinary College, Hawkshead Lane, North Mymms, Herts, AL9 7TA, UK. sfrean@rvc.ac.uk
Abraham
L A
LA
Lees
P
P
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D006736:Horses; D006820:Hyaluronic Acid / Q000494:pharmacology*; D011509:Proteoglycans / Q000096:biosynthesis*
D000276:Adjuvants, Immunologic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D011509:Proteoglycans; D006820:Hyaluronic Acid; C007005:carprofen