In vitro effects of tiaprofenic acid, sodium salicylate and hydrocortisone on the proteoglycan metabolism of human osteoarthritic cartilage.
We examined the in vitro effects of therapeutic doses of tiaprofenic acid (26 micrograms/ml; 2.6 micrograms/ml), sodium salicylate (160 micrograms/ml), and hydrocortisone (7.25 micrograms/ml; 0.725 micrograms/ml) on the proteoglycan metabolism (catabolism and synthesis) and chondrocyte ultrastructure of organ explant cultures of human osteoarthritic (OA) articular cartilage. The effect of these drugs on chondrocyte neutral metalloprotease synthesis was also examined. Tiaprofenic acid and the higher concentration of hydrocortisone had a similar suppressive effect on proteoglycan catabolism (38%). The effect of the lower concentration of hydrocortisone was less marked (29%), while sodium salicylate had the least effect (21%). The proteoglycan released in each treated group was significantly lower (p less than 0.05) than that of the untreated one. The suppression of proteoglycan catabolism by tiaprofenic acid was reversible in all but one specimen. This reversal was only seen in 4 of the 8 patient specimens treated with sodium salicylate and in 2 of the 8 patient specimens treated with the higher dose of hydrocortisone. The decrease in proteoglycan catabolism induced by these drugs correlated with their potential to reduce synthesis of neutral metalloprotease. The proteoglycan synthesis in cartilage organ explant cultures was reduced by sodium salicylate and hydrocortisone, but not by tiaprofenic acid. These findings were corroborated through an electron microscopic study, showing extensive vesicular dilatation of chondrocytic endoplasmic reticulum seen only in explants treated with hydrocortisone or sodium salicylate. Our data suggests that some nonsteroidal antiinflammatory drugs (NSAID) are able to decrease OA cartilage catabolism. However, caution should be taken since certain NSAID, like salicylate, may also possibly jeopardize the cartilage repair process by inhibiting the proteoglycan synthesis.
Pelletier
J P
JP
University of Montreal, PQ, Canada.
Cloutier
J M
JM
Martel-Pelletier
J
J
D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008666:Metalloendopeptidases / Q000096:biosynthesis; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011422:Propionates / Q000494:pharmacology*; D011509:Proteoglycans / Q000378:metabolism*; D012980:Sodium Salicylate / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011422:Propionates; D011509:Proteoglycans; C021270:tiaprofenic acid; D008666:Metalloendopeptidases; D006854:Hydrocortisone; D012980:Sodium Salicylate