Effects of T-2 toxin and selenium on chondrocyte expression of matrix metalloproteinases (MMP-1, MMP-13), α2-macroglobulin (α2M) and TIMPs

被引:30
作者
Chen, Jinghong [1 ]
Chu, Yonglie [1 ]
Cao, Junling [1 ]
Wang, Wei [1 ]
Liu, Jiayuan [1 ]
Wang, Jiali [1 ]
机构
[1] Xi An Jiao Tong Univ, Sch Med, Inst Endem Dis, Lab Environm & Genes Related Dis,Minist Educ, Xian 710061, Shaanxi, Peoples R China
基金
中国国家自然科学基金;
关键词
T-2; toxin; Chondrocyte; Selenium; TIMPs; MMPs; alpha M-2; Kashin-Beck disease; KASHIN-BECK-DISEASE; ARTICULAR-CARTILAGE; ALPHA-2-MACROGLOBULIN; INHIBITOR; COLLAGEN;
D O I
10.1016/j.tiv.2010.12.001
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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.
引用
收藏
页码:492 / 499
页数:8
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