Effects of salicylate and indomethacin on glycosaminoglycan and prostaglandin E2 synthesis in intact canine knee cartilage ex vivo.

The effects of salicylate and indomethacin on glycosaminoglycan synthesis by intact articular cartilage were examined ex vivo. Distal femora of normal dogs were transected at the diaphysis and incubated in medium containing sodium salicylate or indomethacin and 35SO4. Uronic acid contents of habitually loaded and habitually unloaded regions of the condyles averaged 4.2% and 3.1% of the tissue dry weight, respectively. Salicylate had no effect on glycosaminoglycan synthesis in cartilage from loaded sites but suppressed synthesis by 18% (P less than 0.01) in cartilage from unloaded sites, while indomethacin had no effect on glycosaminoglycan synthesis in either region. Evidence that the drugs indeed diffused into the cartilage, even when no effects on glycosaminoglycan metabolism were noted, was provided by measurements of prostaglandin E2. At the concentrations used, both indomethacin and salicylate markedly reduced prostaglandin E2 synthesis by the cartilage. In studies with 14C-acetylsalicylic acid or 14C-indomethacin, the concentration of each drug in cartilage was calculated to be about 3 logs lower than that in the culture medium. Furthermore, drug concentrations in cartilage from loaded zones were consistently lower than those in cartilage from unloaded sites.