摘要目的:探讨T-2毒素、脱氧雪腐镰刀菌烯醇（DON）诱导人软骨细胞差异表达基因与大骨节病（KBD）之间的关系，寻找KBD的潜在分子标志物。方法:采用基因表达谱芯片对T-2毒素（0.01 μg/ml）、DON（1.0 μg/ml）诱导正常人软骨细胞的差异表达基因进行分析，比较其与KBD软骨细胞差异表达基因的异同；并对各组差异表达基因进行KEGG通路富集分析；进一步比较分析T-2毒素、DON诱导人软骨细胞后KBD易感基因的表达情况。结果:基因表达谱芯片分析结果显示，T-2毒素、DON诱导人软骨细胞与正常对照细胞比较分别有882（上调基因349个、下调基因533个）和2 118个差异表达基因（上调基因1 124个、下调基因994个）；与KBD软骨细胞差异表达基因比较，表达趋势一致的基因包括B细胞易位基因1（BTG1）、G蛋白信号调节蛋白5（RGS5）、脂肪酸结合蛋白4（FABP4）和衰老关键蛋白1（FBLN1），相同的KEGG通路包括p53、细胞外基质受体相互作用和磷脂酰肌醇3-激酶-蛋白激酶B（PI3K-Akt）信号通路。T-2毒素、DON诱导人软骨细胞均可引起KBD易感基因生长分化因子5（GDF5）表达上调、Ⅸ型胶原A1（COL9A1）表达下调。结论:BTG1、RGS5、FABP4、FBLN1、GDF5及COL9A1基因在KBD发病中有重要作用，可作为KBD病因机制的潜在分子标志物。

abstractsObjective:To investigate the relationship between T-2 toxin, deoxynivalenol (DON) induced differentially expressed genes in human chondrocytes and Kashin-Beck disease (KBD), and to search for potential molecular markers of KBD.Methods:Gene microarray profiling was used to analyze the differentially expressed genes induced by T-2 toxin (0.01 μg/ml) and DON (1.0 μg/ml) in normal human chondrocytes, and the differences and similarities between them and the differentially expressed genes in KBD chondrocytes were compared. KEGG pathway enrichment analysis was performed on differentially expressed genes in each group. And the expression patterns of KBD susceptibility genes in T-2 toxin and DON induced human chondrocytes were further compared and analyzed.Results:Gene microarray profiling analysis showed that there were 882 (349 up-regulated genes, 533 down-regulated genes) and 2 118 differentially expressed genes (1 124 up-regulated genes, 994 down-regulated genes) in human chondrocytes induced by T-2 toxin and DON compared with normal control cells, respectively. Compared with differentially expressed genes in KBD chondrocytes, the genes with the same expression trend included B cell translocation gene 1 (BTG1), G protein signaling regulatory protein 5 (RGS5), fatty acid binding protein 4 (FABP4) and key protein senescence 1 (FBLN1), the same KEGG pathway including p53, extracellular matrix receptor interaction and phosphatidylinositol-3-kinase-protein kinase B (PI3K-Akt) signaling pathway. Both T-2 toxin and DON induced human chondrocytes to up-regulate the expression of KBD susceptibility gene growth differentiation factor 5 (GDF5) and down-regulate the expression of collagen type ⅨA1 (COL9A1).Conclusion:The BTG1, RGS5, FABP4, FBLN1, GDF5 and COL9A1 genes play an important role in the pathogenesis of KBD and can be used as potential molecular markers for the pathogenesis of KBD.