Celecoxib has a positive effect on the overall metabolism of hyaluronan and proteoglycans in human osteoarthritic cartilage.
OBJECTIVE
To assess the effects of celecoxib, a cyclooxygenase (COX-2) selective inhibitor, on the metabolism of hyaluronan (HA) and proteoglycans (PG) in human cartilage explants with midrange severity of osteoarthritis (OA). Results were compared with those of diclofenac, a non-selective COX inhibitor.


METHODS
Cartilage specimens (OA grade 4-8 on Mankin's scale) were pulsed with 3H -glucosamine and chased in the absence or presence of 1-10 micro g/ml of celecoxib or diclofenac. After papain digestion, the labeled chondroitin sulfate and HA molecules were purified by anion-exchange chromatography.


RESULTS
Diclofenac did not affect the metabolic balance of PG and HA whereas, in a relatively dose-dependent manner, celecoxib increased the synthesis of HA and PG; celecoxib also reduced the net loss of labeled HA and PG molecules from cartilage explants.


CONCLUSIONS
In short term in vitro cultures, celecoxib has a favorable effect on the overall metabolism of PG and HA. It is therefore unlikely that this drug would have a detrimental effect on articular cartilage during longterm administration. Further, celecoxib might help counteract the depletion of HA seen in OA cartilage.
El Hajjaji
Hafida
H
ICP Christian de Duve Institute of Cellular Pathology and the Department of Rheumatology, Saint-Luc University Hospital, Catholic University of Louvain, Avenue Mounier, 1200 Brussels, Belgium.
Marcelis
Annette
A
Devogelaer
Jean-Pierre
JP
Manicourt
Daniel-Henri
DH
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D000068579:Celecoxib; D004008:Diclofenac / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism*; D011509:Proteoglycans / Q000096:biosynthesis / Q000378:metabolism*; D011720:Pyrazoles; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011509:Proteoglycans; D011720:Pyrazoles; D013449:Sulfonamides; D004008:Diclofenac; D006820:Hyaluronic Acid; D000068579:Celecoxib