β-catenin regulates expression of cyclooxygenase-2 in articular chondrocytes

β-catenin regulates expression of cyclooxygenase-2 in articular chondrocytes
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DOI:
10.1016/s0006-291x(02)00824-0
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发表时间:
2002-08-09
影响因子:
3.1
通讯作者:
Chun, JS
Chun, JS
中科院分区:
生物学4区
文献类型:
--
作者:
Kim, SJ;Im, DS;Chun, JS

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促炎细胞因子如白细胞介素(IL)-1 β通过诱导环氧合酶(考克斯)-2表达引起关节软骨炎症。我们在这项研究中研究了β-连环蛋白在IL-1 β调节关节软骨细胞考克斯-2表达中的作用。IL-1 β增加考克斯-2的表达,并诱导转录活性β-连环蛋白的积累和核转位。通过用LiCl或蛋白酶体抑制剂处理细胞来抑制β-连环蛋白降解刺激了考克斯-2的表达,表明转录活性β-连环蛋白足以诱导考克斯-2表达。通过观察到转录活性β-连环蛋白的异位表达刺激了考克斯-2的表达,进一步证明了这一点。β-catenin和考克斯-2蛋白在骨关节炎和类风湿关节炎软骨中的水平增加,表明β-catenin可能在关节炎软骨的炎症反应中起作用。综上所述,我们的数据表明,转录活性β-连环蛋白的积累有助于考克斯-2在关节软骨细胞中的表达。(C)2002 Elsevier Science(美国)。All rights reserved.
Pro-inflammatory cytokine such as interleukin (IL)-1beta causes inflammation of articular cartilage via induction of cyclooxygenase (COX)-2 expression. We investigated in this study the role of beta-catenin in the IL-1beta regulation of COX-2 expression in articular chondrocytes. IL-1beta increased expression of COX-2 and induced accumulation and nuclear translocation of transcriptionally competent beta-catenin. Inhibition of beta-catenin degradation by the treatment of cells with LiCl or proteasome inhibitor stimulated expression of COX-2, indicating that transcriptionally active beta-catenin is sufficient to induce COX-2 expression. This was demonstrated further by the observation that ectopic expression of transcriptionally competent beta-catenin stimulated expression of COX-2. Levels of beta-catenin and COX-2 protein were increased in osteoarthritic and rheumatoid arthritic cartilage, suggesting that beta-catenin may play a role in the inflammatory responses of arthritic cartilage. Taken together, our data suggest that accumulation of transcriptionally active beta-catenin contributes to the expression of COX-2 in articular chondrocytes. (C) 2002 Elsevier Science (USA). All rights reserved.