Regulation of nitric oxide production by salicylates and tenidap in human OA-affected cartilage, rat chondrosarcomas and bovine chondrocytes.
OBJECTIVE
To examine the effects of non-steroidal anti-inflammatory drugs (NSAIDS) on nitric oxide (NO) and prostaglandin E2 (PGE2) production in chondrocytes from three different species.


METHODS
We have estimated NO production by Griess method, and PGE2 by RIA from the supernatants of articular cartilage obtained from osteoarthritis joints (OA-affected cartilage), rat chondrosarcomas (in ex vivo conditions) and bovine chondrocytes (stimulated with cytokines + endotoxin in vitro conditions) in the presence or absence of aspirin, indomethacin, sodium salicylate, tenidap and glucocorticoids.


RESULTS
NO, which was spontaneously released in ex vivo conditions by OA-affected cartilage and rat chondrosarcomas (maintained in vivo), was susceptible to inhibition by pharmacologically relevant concentrations of aspirin, sodium salicylate and tenidap, but not to concentrations of indomethacin or glucocorticoids that significantly inhibited PGE2 production under the same conditions. Similarly, the production of NO by bovine chondrocytes grown in monolayer cultures that had been stimulated with cytokines + endotoxins (in vitro) to release both NO and PGE2 (at 48-72 h post stimulation), were inhibited by aspirin, sodium salicylate and tenidap, but not by indomethacin or glucocorticoids at concentrations sufficient to PGE2 production. Inhibition of NO in the cytokines + endotoxin stimulated bovine chondrocytes (like the human OA-affected cartilage) augmented PGE2 production.


CONCLUSIONS
These experiments demonstrate that NO production by chondrocytes across species show a similar profile of susceptibility to inhibition by selected anti-inflammatory drugs. The insensitivity of NO production to glucocorticoids is an important characteristics of these cells that merits further investigation.
Attur
M G
MG
Department of Rheumatology, Hospital for Joint Diseases, New York, New York 10003, USA.
Patel
R
R
DiCesare
P E
PE
Steiner
G C
GC
Abramson
S B
SB
Amin
A R
AR
D000368:Aged; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D002813:Chondrosarcoma / Q000378:metabolism; D046508:Culture Techniques; D016207:Cytokines / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology; D000078183:Oxindoles; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000494:pharmacology; D013045:Species Specificity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004731:Endotoxins; D007211:Indoles; D000078183:Oxindoles; D012459:Salicylates; D009569:Nitric Oxide; C062866:tenidap; D019001:Nitric Oxide Synthase