Effects of T-2 toxin and selenium on chondrocyte expression of matrix metalloproteinases (MMP-1, MMP-13), α2-macroglobulin (α2M) and TIMPs
Effects of T-2 toxin and selenium on chondrocyte expression of matrix metalloproteinases (MMP-1, MMP-13), α2-macroglobulin (α2M) and TIMPs
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DOI：
10.1016/j.tiv.2010.12.001
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发表时间：
2011-03-01
影响因子：
3.2
通讯作者：
Wang, Jiali
中科院分区：
文献类型：
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作者：
Chen, Jinghong;Chu, Yonglie;Wang, Jiali
T-2毒素被认为是大骨节病的重要致病因素，补硒可部分预防大骨节病。本文研究了T-2毒素对体外培养的人软骨细胞Ⅱ型胶原降解的影响。分离人软骨细胞，将其培养在骨基质明胶上，形成体外人工软骨模型，并与T-2毒素和硒进行比较。免疫组织化学分析表明，T-2毒素减少II型胶原染色和硒似乎可以防止T-2毒素诱导的工程软骨中II型胶原的减少。Western blot和RT-PCR分析显示T-2毒素可诱导MMP-13和MMP-1表达增加，而一般性内蛋白酶抑制剂（α M-2）表达减少。明胶反向酶谱显示T-2毒素暴露后TIMP-1和TIMP-2水平呈剂量依赖性降低。硒通过下调MMP-13蛋白和mRNA表达，上调TIMP-1和TIMP-2表达，增加II型胶原蛋白水平，发挥保护作用。这些数据表明T-2毒素通过上调MMP-13和TIMP-1以及下调TIMP-2和α M-2表达来诱导软骨基质降解。皇冠版权所有（c）2010由爱思唯尔有限公司出版。保留所有权利。
T-2 toxin is regarded as an important etiological factor of Kashin-Beck disease, and supplementation of selenium-salt partly prevents Kashin-Beck disease. The present study investigated the effects of T-2 toxin on the degradation of type II collagen in human chondrocytes in vitro. Human chondrocytes were isolated and cultured on bone matrix gelatin to form an artificial cartilage model in vitro with or without T-2 toxin and selenium. Immunohistochemistry analyses showed that T-2 toxin decreased type II collagen staining and selenium appeared to prevent the decrease in type II collagen induced by T-2 toxin in engineered cartilage. Then, Western blot and RT-PCR analyses showed that an increase in MMP-13 and MMP-1 expressions, and a decrease in the expression of the general endoproteinase inhibitor (alpha M-2) were induced by T-2 toxin. Gelatin reverse zymography showed that TIMP-1 and TIMP-2 levels were decreased in a dose-dependent manner after exposure of T-2 toxin. Selenium had a protective role by increasing the level of type II collagen protein through down-regulation of MMP-13 protein and mRNA expression and up-regulation of TIMP-1 and TIMP-2 expressions. These data suggest T-2 toxin induces cartilage matrix degradation by the up-regulation of MMP-13 and TIMP-1, and down-regulation of TIMP-2 and alpha M-2 expressions. Crown Copyright (c) 2010 Published by Elsevier Ltd. All rights reserved.