Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Faculty of Public Health, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China, 710061.
BMC Musculoskelet Disord. 2012 Jul 24;13:130. doi: 10.1186/1471-2474-13-130.
Kashin-Beck Disease (KBD) is an endemic osteochondropathy. Mycotoxins are believed to play an important role in the pathogenesis of KBD. Because the molecular mechanism of mycotoxin-induced cartilage lesions remains unclear, there is not effective treatment for KBD now. To identify key genes involved in the mycotoxin-induced cartilage lesions, we compared the expression profiles of mycotoxin-related genes (MRG) between KBD cartilage and healthy cartilage.
Total RNA was isolated from cartilage samples, following by being amplified, labeled and hybridized to Agilent human whole genome microarray chip. qRT-PCR was conducted to validate the microarray data. 1,167 MRG were derived from the environmentally related genomic database Toxicogenomics. The microarray data of MRG was subjected to single gene and gene ontology (GO) expression analysis for identifying differently expressed genes and GO.
We identified 7 up-regulated MRG and 2 down-regulated MRG in KBD cartilage, involved in collagen, apoptosis, metabolism and growth & development. GO expression analysis found that 4 apoptosis-related GO and 5 growth & development-related GO were significantly up-regulated in KBD cartilage.
Based on the results of previous and our studies, we suggest that mycotoxins might contribute to the development of KBD through dysfunction of MRG involved in collagen, apoptosis and growth & development in cartilage.
大骨节病(KBD)是一种地方性软骨病。霉菌毒素被认为在 KBD 的发病机制中起重要作用。由于霉菌毒素诱导的软骨损伤的分子机制尚不清楚,目前尚无有效的 KBD 治疗方法。为了鉴定与霉菌毒素诱导的软骨损伤相关的关键基因,我们比较了 KBD 软骨和健康软骨中与霉菌毒素相关的基因(MRG)的表达谱。
从软骨样本中分离总 RNA,进行扩增、标记和与 Agilent 人类全基因组微阵列芯片杂交。进行 qRT-PCR 验证微阵列数据。从环境相关基因组数据库 Toxicogenomics 中得到 1167 个 MRG。对 MRG 的微阵列数据进行单基因和基因本体论(GO)表达分析,以鉴定差异表达基因和 GO。
我们在 KBD 软骨中鉴定出 7 个上调的 MRG 和 2 个下调的 MRG,涉及胶原、凋亡、代谢和生长发育。GO 表达分析发现,KBD 软骨中 4 个与凋亡相关的 GO 和 5 个与生长发育相关的 GO 显著上调。
基于先前和我们的研究结果,我们认为霉菌毒素可能通过参与胶原、凋亡和软骨生长发育的 MRG 功能障碍导致 KBD 的发生。