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The effect of cyclooxygenase-2 selective inhibitors on the proliferation and apoptosis of human articular chondrocytes
Arthritis Res Thervolume 5, Article number: 56 (2003)
Cyclooxygenase-2 (COX-2) selective inhibitors are being widely used in the treatment of osteoarthritis, with their favorable efficacy and safe profiles. The proliferative role of COX-2 has been recognized in several human cancers and its inhibitors were found to induce apoptosis in these cancer cells. Since the apoptosis of chondrocytes is an important contributor to the development of the osteoarthritis, we determined to investigate the effect of selective COX-2 inhibitors on the proliferation and apoptosis of human chondrocytes.
Human chondrocytes from osteoarthritis patients were treated with selective COX-2 inhibitors (celecoxib, MF-tricyclic) and nonselective inhibitors (sulindac and indomethacin) under various conditions. Cell proliferation was assessed by MTT assay and the apoptosis was quantified by flow cytometry analysis after propidium iodide staining.
The COX-2 selective inhibitor celecoxib strongly inhibited the proliferation of chondrocytes in a dose-dependent and time-dependent manner. When compared with dimethylsulfoxide controls, chondrocytes proliferated 49.1 ± 9.7% under 40 μg/ml celecoxib, 80.4 ± 28.3% under 40 μ/ml sulindac sulfide, 93.1 ± 13.3% under 40 μg/ml indomethacin and 113.7 ± 8.9% under another COX-2 selective inhibitor, MF-tricyclic. Incubation with 80 μg/ml celecoxib for 12 hours lead to apoptosis in 6.6% of the chondrocytes, while incubation with 80 μg/ml MF-tricyclic lead to apoptosis in 4.8% of the cells.
In this study, we found that the COX-2 selective inhibitor celecoxib could inhibit proliferation of chondrocytes from osteoarthritis patients, while another COX-2 selective inhibitor, MF-tricyclic, does not affect the proliferation of the cells. Further study will be warranted on the clinical effects of different COX-2 selective inhibitors in osteoarthritis patients. Furthermore, our results suggest that celecoxib may induce apoptosis of chondrocytes via other pathways than COX-2 inhibition.