Genome-wide gene expression analysis suggests an important role of hypoxia in the pathogenesis of endemic osteochondropathy Kashin-Beck disease.
Genome-wide gene expression analysis suggests an important role of hypoxia in the pathogenesis of endemic osteochondropathy Kashin-Beck disease.
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DOI：
10.1371/journal.pone.0022983
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Li C
中科院分区：
文献类型：
--
作者：
Zhang F;Guo X;Wang W;Yan H;Li C
大骨节病是一种地方性骨软骨病，其发病机制目前尚不清楚。在这项研究中，我们比较了基因表达谱分别来自大骨节病患者和正常对照关节软骨。提取总RNA，扩增，标记，与Agilent人1A 22 k全基因组芯片杂交。进行qRT-PCR以验证我们的微阵列数据。在大骨节病软骨组织中共检测到57个上调基因（比值≥2.0）和24个下调基因（比值≤0.5）。为进一步明确大骨节病发病机制中的关键基因，应用Bayesian方差分析（BAM）软件，筛选出12个潜在的关键基因，平均比值为6.64，分别涉及细胞凋亡、代谢、细胞因子和生长因子以及细胞骨架和细胞运动。使用基因集富集分析（GSEA）软件来鉴定不同表达的基因本体类别和途径。GSEA结果显示，与正常对照组相比，大骨节病患者的一组与细胞凋亡、缺氧和线粒体功能相关的基因本体类别和通路显著上调。根据本研究结果，我们认为慢性缺氧引起的线粒体损伤和细胞凋亡可能在大骨节病的发病机制中起重要作用。我们的努力可能有助于了解大骨节病的发病机制，以及其他骨关节病与类似的关节软骨病变。
Kashin-Beck Disease (KBD) is an endemic osteochondropathy, the pathogenesis of which remains unclear now. In this study, we compared gene expression profiles of articular cartilage derived respectively from KBD patients and normal controls. Total RNA were isolated, amplified, labeled and hybridized to Agilent human 1A 22 k whole genome microarray chip. qRT-PCR was conducted to validate our microarray data. We detected 57 up-regulated genes (ratios ≥2.0) and 24 down-regulated genes (ratios ≤0.5) in KBD cartilage. To further identify the key genes involved in the pathogenesis of KBD, Bayesian analysis of variance for microarrays(BAM) software was applied and identified 12 potential key genes with an average ratio 6.64, involved in apoptosis, metabolism, cytokine & growth factor and cytoskeleton & cell movement. Gene Set Enrichment Analysis (GSEA) software was used to identify differently expressed gene ontology categories and pathways. GSEA found that a set of apoptosis, hypoxia and mitochondrial function related gene ontology categories and pathways were significantly up-regulated in KBD compared to normal controls. Based on the results of this study, we suggest that chronic hypoxia-induced mitochondrial damage and apoptosis might play an important role in the pathogenesis of KBD. Our efforts may help to understand the pathogenesis of KBD as well as other osteoarthrosis with similar articular cartilage lesions.
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影响因子：
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