Institute of Endemic Diseases, Medical School of Xi'an Jiaotong University, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, PR China.
Toxicol In Vitro. 2011 Mar;25(2):492-9. doi: 10.1016/j.tiv.2010.12.001. Epub 2010 Dec 7.
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 (α(2)M) 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 α(2)M expressions.
T-2 毒素被认为是大骨节病的重要病因之一，而补硒可部分预防大骨节病。本研究探讨了 T-2 毒素对体外人软骨细胞 II 型胶原降解的影响。体外用人软骨细胞在骨基质明胶上分离培养，形成人工软骨模型，加入或不加入 T-2 毒素和硒。免疫组化分析表明，T-2 毒素降低了 II 型胶原的染色，而硒似乎可预防 T-2 毒素引起的工程软骨中 II 型胶原的减少。然后，Western blot 和 RT-PCR 分析表明，T-2 毒素诱导 MMP-13 和 MMP-1 表达增加，而一般内肽酶抑制剂 (α(2)M) 的表达减少。明胶反转酶谱分析表明，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 表达以及上调 TIMP-1 和 TIMP-2 表达，通过增加 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 和下调 TIMP-2 和 α(2)M 的表达诱导软骨基质降解。
