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

International Journal of Molecular Sciences

Kousuke Kumagai²  Mitsuhiko Kubo²  Shinji Imai²  Futoshi Toyoda¹  Tsutomu Maeda²  Noriaki Okumura²  Hiroshi Matsuura¹ 

[1] Department of Physiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan; E-Mails:;Department of Orthopaedic Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan; E-Mails:

关键词: chondrocyte;    apoptosis;    TNFα;    COX-2;    osteoarthritis;   

DOI  :  10.3390/ijms141019705

来源: mdpi

【 摘 要 】

Chondrocyte apoptosis contributes to the disruption of cartilage integrity in osteoarthritis (OA). Recently, we reported that activation of volume-sensitive Cl⁻ current (I_Cl,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 I_Cl,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 I_Cl,vol. Pretreatment of cells with selective COX-2 blocker etodolac markedly inhibited I_Cl,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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland