The COX-2 selective blocker etodolac inhibits TNFα-induced apoptosis in isolated rabbit articular chondrocytes.
The COX-2 selective blocker etodolac inhibits TNFα-induced apoptosis in isolated rabbit articular chondrocytes.
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DOI：
10.3390/ijms141019705
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发表时间：
2013-09-30
影响因子：
5.6
通讯作者：
Matsusue Y
中科院分区：
文献类型：
--
作者：
Kumagai K;Kubo M;Imai S;Toyoda F;Maeda T;Okumura N;Matsuura H;Matsusue Y
软骨细胞凋亡有助于骨关节炎（OA）软骨完整性的破坏。最近，我们报道了体积敏感Cl -电流（ICl,vol）的激活介导细胞收缩，引发兔关节软骨细胞凋亡。环氧合酶（COX）阻滞剂常用于OA的治疗。在本研究中，我们使用膜片钳技术检测了COX选择性阻滞剂对tnf α-诱导的兔软骨细胞ICl，vol活化的体外影响。将分离的软骨细胞暴露于TNFα后，膜Cl -电导明显增加。tnf α诱发的Cl -电流表现出与ICl相似的电生理和药理学特性。选择性COX-2阻滞剂依托度酸对细胞进行预处理可显著抑制ICl、TNFα对细胞体积的激活以及随后的凋亡事件，如凋亡细胞体积减少（AVD）和caspase-3/7活性升高。相比之下，COX-1阻滞剂对TNFα诱导的细胞体积减少或caspase-3/7活性增加没有影响。由此可见，cox -2选择性阻断剂对tnf α-诱导的凋亡事件具有抑制作用，提示该药物对OA具有治疗作用。
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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影响因子：
7.3
作者：
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通讯作者：
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