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Int. J. Mol. Sci. 2013, 14(10), 19705-19715; doi:10.3390/ijms141019705

The COX-2 Selective Blocker Etodolac Inhibits TNFα-Induced Apoptosis in Isolated Rabbit Articular Chondrocytes

Department of Orthopaedic Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
Department of Physiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
Author to whom correspondence should be addressed.
Received: 31 July 2013 / Revised: 6 September 2013 / Accepted: 10 September 2013 / Published: 30 September 2013
(This article belongs to the Special Issue The Chondrocyte Phenotype in Cartilage Biology)
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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. View Full-Text
Keywords: chondrocyte; apoptosis; TNFα; COX-2; osteoarthritis chondrocyte; apoptosis; TNFα; COX-2; osteoarthritis

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Kumagai, K.; Kubo, M.; Imai, S.; Toyoda, F.; Maeda, T.; Okumura, N.; Matsuura, H.; Matsusue, Y. The COX-2 Selective Blocker Etodolac Inhibits TNFα-Induced Apoptosis in Isolated Rabbit Articular Chondrocytes. Int. J. Mol. Sci. 2013, 14, 19705-19715.

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