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Increased Chondrocyte Apoptosis Is Associated with Progression of Osteoarthritis in Spontaneous Guinea Pig Models of the Disease
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

1,2,* , 1
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.
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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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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