Effect of tenidap on cartilage integrity in vitro.
OBJECTIVE
The maintenance of articular cartilage integrity during long term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is of clinical importance. These experiments were set up to test the action of tenidap, naproxen, and diclofenac on bovine and porcine cartilage, matrix synthesis, and catabolism.


METHODS
Short term organ culture techniques were used to determine the effect of interleukin 1 (IL-1) on synthesis and degradation, and the action of tenidap and the other drugs on these parameters. The retention of glycosaminoglycans (GAGs) and the synthesis of GAGs by incorporation of sulphur-35 labelled sulphate was used to determine the chondrocyte metabolic activity.


RESULTS
The action of human recombinant interleukin 1 alpha (hrIL-1 alpha) in increasing catabolic activity and inhibiting synthetic activity of the animal cartilages was confirmed. Tenidap was shown to give substantial and significant protection against the catabolic effects of hrIL-1 alpha and, to a lesser degree, against the inhibition of matrix synthesis by the cytokine. Neither diclofenac nor naproxen in doses expected to occur in the synovial fluid showed this action. Tenidap also inhibited the GAG loss from cocultures and, to a moderate degree, reversed the inhibition of synthesis by synovial tissue. Tenidap also stimulated cartilage repair activity during recovery from IL-1 treatment. The optimum concentration of the action against IL-1 was between 5 and 10 micrograms/ml. Above this concentration tenidap itself showed some inhibitory action on GAG synthesis.


CONCLUSIONS
Bearing in mind the problems in extrapolating from in vitro work on animal cartilages to humans, it seems possible that tenidap may be useful in decreasing the deleterious action of cytokines such as IL-1 on cartilage integrity during arthritic disease and in stimulating chondrocyte repair processes.
Dingle
J T
JT
Strangeways Laboratory, Cambridge, United Kingdom.
Leeming
M R
MR
Martindale
J J
JJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D004008:Diclofenac / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000096:biosynthesis; D007211:Indoles / Q000494:pharmacology*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009288:Naproxen / Q000494:pharmacology; D009924:Organ Culture Techniques; D000078183:Oxindoles; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine; D013583:Synovial Membrane / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006025:Glycosaminoglycans; D007211:Indoles; D007375:Interleukin-1; D000078183:Oxindoles; D011994:Recombinant Proteins; D004008:Diclofenac; D009288:Naproxen; C062866:tenidap