The COX-2 Selective Blocker Etodolac Inhibits TNFα-Induced Apoptosis in Isolated Rabbit Articular Chondrocytes |
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| Authors: | Kousuke Kumagai Mitsuhiko Kubo Shinji Imai Futoshi Toyoda Tsutomu Maeda Noriaki Okumura Hiroshi Matsuura Yoshitaka Matsusue |
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| Affiliation: | 1.Department of Orthopaedic Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan; E-Mails: (M.K.); (S.I.); (T.M.); (N.O.); (Y.M.);2.Department of Physiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan; E-Mails: (F.T.); (H.M.) |
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| Abstract: | Chondrocyte apoptosis contributes to the disruption of cartilage integrity in osteoarthritis (OA). Recently, we reported that activation of volume-sensitive Cl− current (ICl,vol) mediates cell shrinkage, triggering apoptosis in rabbit articular chondrocytes. A cyclooxygenase (COX) blocker is frequently used for the treatment of OA. In the present study, we examined in vitro effects of selective blockers of COX on the TNFα-induced activation of ICl,vol in rabbit chondrocytes using the patch-clamp technique. Exposure of isolated chondrocytes to TNFα resulted in an obvious increase in membrane Cl− conductance. The TNFα-evoked Cl− current exhibited electrophysiological and pharmacological properties similar to those of ICl,vol. Pretreatment of cells with selective COX-2 blocker etodolac markedly inhibited ICl,vol activation by TNFα as well as subsequent apoptotic events such as apoptotic cell volume decrease (AVD) and elevation of caspase-3/7 activity. In contrast, a COX-1 blocker had no effect on the decrease in cell volume or the increase in caspase-3/7 activity induced by TNFα. Thus, the COX-2-selective blocker had an inhibitory effect on TNFα-induced apoptotic events, which suggests that this drug would have efficacy for the treatment of OA. |
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| Keywords: | chondrocyte apoptosis TNFα COX-2 osteoarthritis |
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