The COX-2 selective blocker etodolac inhibits TNFα-induced apoptosis in isolated rabbit articular chondrocytes

• Published in: International journal of molecular sciences Vol. 14; no. 10; pp. 19705 - 19715
• Main Authors: Kumagai, Kousuke, Kubo, Mitsuhiko, Imai, Shinji, Toyoda, Futoshi, Maeda, Tsutomu, Okumura, Noriaki, Matsuura, Hiroshi, Matsusue, Yoshitaka
• Format: Journal Article
• Language: English
• Published: Switzerland Molecular Diversity Preservation International (MDPI) 30.09.2013; MDPI AG
• Subjects: Animals; apoptosis; Apoptosis - drug effects; Caspase 3 - metabolism; Caspase 7 - metabolism; Chlorides - metabolism; chondrocyte; Chondrocytes - drug effects; Chondrocytes - metabolism; COX-2; Cyclooxygenase 1 - metabolism; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - pharmacology; Male; osteoarthritis; Rabbits; TNFα; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1422-0067; 1422-0067
• DOI: 10.3390/ijms141019705

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.