Thiram is a kind of organic compound, which is commonly used for sterilization, insecticidal and deodorization in daily life. Its toxicology has been broadly studied. Recently, more and more microRNAs have been shown to participate in the regulation of cartilage development. However, the potential mechanism by which microRNA regulates chondrocyte growth is still unclear. Our experiments have demonstrated that thiram can hamper chondrocytes development and cause a significant increase in miR-203a content in vitro and in vivo trials. miR-203a mimic significantly decrease in mRNA and protein expression of Wnt4, Runx2, COL2A1, β-catenin and ALP, and significantly enhance the mRNA and protein levels of GSK-3β. It has been observed that overexpression of miR-203a hindered chondrocytes development. In addition, Runx2 was confirmed to be a direct target of miR-203a by dual luciferase report gene assay. Transfection of si-Runx2 into chondrocytes reveals that significant downregulation of genes is associated with cartilage development. Overall, these results suggest that overexpression of miR-203a inhibits the expression of Runx2. These findings are conducive to elucidate the mechanism of chondrocytes dysplasia induced by thiram and provide new research ideas for the toxicology of thiram.

中文翻译：

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miR-203a靶向Runx2调控福美双诱导软骨细胞发育的分子机制

福美双是一种有机化合物，在日常生活中常用于杀菌、杀虫、除臭等作用。其毒理学已得到广泛研究。近年来，越来越多的microRNA被证明参与软骨发育的调控。然而，microRNA调节软骨细胞生长的潜在机制仍不清楚。我们的实验表明，在体外和体内试验中，福美双可以阻碍软骨细胞发育并导致 miR-203a 含量显着增加。 miR-203a 模拟物显着降低 Wnt4、Runx2、COL2A1、β-catenin 和 ALP 的 mRNA 和蛋白表达，并显着增强 GSK-3β 的 mRNA 和蛋白水平。据观察，miR-203a 的过度表达会阻碍软骨细胞的发育。此外，通过双荧光素酶报告基因检测证实Runx2是miR-203a的直接靶标。将 si-Runx2 转染到软骨细胞中表明基因的显着下调与软骨发育相关。总体而言，这些结果表明 miR-203a 的过表达会抑制 Runx2 的表达。这些研究结果有利于阐明福美双引起软骨细胞发育不良的机制，并为福美双的毒理学提供新的研究思路。