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


: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.


Int J Mol Sci


Kumagai K,Kubo M,Imai S,Toyoda F,Maeda T,Okumura N,Matsuura H,Matsusue Y




Has Abstract


2013-09-30 00:00:00












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    pub_type: 杂志文章


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    authors: Mirossay L,Varinská L,Mojžiš J

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    journal_title:International journal of molecular sciences

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    authors: Villani P,Fresegna AM,Ranaldi R,Eleuteri P,Paris L,Pacchierotti F,Cordelli E

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


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    journal_title:International journal of molecular sciences

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    pub_type: 杂志文章,评审


    authors: Tukaj S

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    authors: Chen X,Huang Z,Wang H,Jia G,Liu G,Guo X,Tang R,Long D

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Ling SSM,Chen YT,Wang J,Richards AM,Liew OW

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Yuan J,Cao JY,Tang ZL,Wang N,Li K

    更新日期:2011-01-01 00:00:00

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Bica I,Bunoiu OM

    更新日期:2019-08-27 00:00:00

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Ranieri M

    更新日期:2019-10-27 00:00:00

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Smolikova G,Dolgikh E,Vikhnina M,Frolov A,Medvedev S

    更新日期:2017-09-16 00:00:00

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: García-Ibañez P,Yepes-Molina L,Ruiz-Alcaraz AJ,Martínez-Esparza M,Moreno DA,Carvajal M,García-Peñarrubia P

    更新日期:2020-12-10 00:00:00

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Mei S,Liu T,Wang Z

    更新日期:2016-01-06 00:00:00