Selective COX-2 inhibition prevents proinflammatory cytokine-induced cartilage damage.
OBJECTIVE
This study evaluated the in vitro effect of the selective cyclooxygenase-2 (COX) inhibitor celecoxib on cartilage matrix turnover under normal and inflammatory conditions.


METHODS
Healthy human articular cartilage tissue alone, in co-culture with peripheral blood mononuclear cells (PBMC) or in the presence of interleukin 1 (IL-1beta) plus tumour necrosis factor alpha (TNF-alpha) was cultured for 7 days in the presence of celecoxib. Changes in cartilage matrix turnover were measured.


RESULTS
No direct effects of celecoxib on healthy normal cartilage were found. Both PBMC and IL-1beta plus TNF-alpha induced strong inhibition of cartilage proteoglycan synthesis and significant enhancement of the release of proteoglycans, diminishing proteoglycan content. Celecoxib was able to reverse these adverse effects up to complete normalization.


CONCLUSIONS
The results suggest that, under the influence of inflammation, COX-2 is up-regulated, which results in disturbance of cartilage matrix turnover. Celecoxib, by diminishing COX-2 activity, prevents these adverse effects without having a direct effect on healthy cartilage.
Mastbergen
S C
SC
Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Lafeber
F P J G
FP
Bijlsma
J W J
JW
D000368:Aged; D064236:Cartilage Oligomeric Matrix Protein; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D000068579:Celecoxib; D002478:Cells, Cultured; D018920:Coculture Techniques; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D064235:Matrilin Proteins; D011509:Proteoglycans / Q000096:biosynthesis; D011720:Pyrazoles; D013449:Sulfonamides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D064236:Cartilage Oligomeric Matrix Protein; D016861:Cyclooxygenase Inhibitors; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D007375:Interleukin-1; D064235:Matrilin Proteins; D011509:Proteoglycans; D011720:Pyrazoles; D013449:Sulfonamides; C577553:TSP5 protein, human; D014409:Tumor Necrosis Factor-alpha; D000068579:Celecoxib