Abstract: Celecoxib Has a Positive Effect on the Overall Metabolism of Hyaluronan and Proteoglycans in Human Osteoarthritic Cartilage

Celecoxib Has a Positive Effect on the Overall Metabolism of Hyaluronan and Proteoglycans in Human Osteoarthritic Cartilage

HAFIDA EL HAJJAJI, ANNETTE MARCELIS, JEAN-PIERRE DEVOGELAER, and DANIEL-HENRI MANICOURT

ABSTRACT.

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 µg/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.

Conclusion. 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. (J Rheumatol 2003;30:2444-51)

Key Indexing Terms:

CARTILAGE
CELECOXIB
DICLOFENAC
PROTEOGLYCANS
HYALURONAN

From the ICP Christian de Duve Institute of Cellular Pathology and the Department of Rheumatology, Saint-Luc University Hospital, Catholic University of Louvain, Brussels, Belgium.

Supported by Grant 3.4597.02 of the Fonds de la Recherche Scientifique Médicale (Belgium).

H. El Hajjaji, Doctoral Student; A. Marcelis, Laboratory Technician, ICP Christian de Duve Institute of Cellular Pathology; J-P. Devogelaer, Professor of Medicine, Department of Rheumatology, Saint-Luc University Hospital; D-H. Manicourt, Professor of Medicine, Head of the Connective Tissue Unit, ICP Christian de Duve Institute of Cellular Pathology and Department of Rheumatology, Saint-Luc University Hospital.

Address reprint requests to Dr. D-H. Manicourt, Department of Rheumatology, UCL 5390, Avenue Mounier, 1200 Brussels, Belgium.

Submitted September 17, 2002; revision accepted March 26, 2003.