骨关节炎患者膝关节滑膜组织的基因表达谱分析

Gene expression profile of knee joint synovial tissue in patients with osteoarthritis

目的:分析骨关节炎患者膝关节滑膜组织的基因表达谱。方法:从公共基因芯片数据库选取芯片数据,利用GEO2R筛选骨关节炎患者滑膜组织和正常滑膜组织的差异表达基因;对筛选出的基因进行GO功能和KEEG通路富集分析,利用STRING数据库及Cytoscape软件构建蛋白间相互作用网络,筛选关键基因。结果:纳入数据库中两组基因芯片数据,共筛选出131个共同差异表达基因,其中上调基因98个,下调基因33个。GO富集分析提示,差异基因主要在细胞粘附、对成纤维细胞生长因子刺激的反应、细胞内受体信号通路等功能富集。KEGG富集结果显示,差异表达基因参与了丝裂原活化蛋白激酶、低氧诱导因子-1、磷脂酰肌醇3激酶/蛋白激酶B等信号通路。蛋白间相互作用网络提示了10个关键基因。结论:通过对OA基因表达谱分析筛选差异表达基因发现OA的发病机制不仅与细胞增殖、病理性血管生成、炎症刺激等有关,更是多信号通路、多靶点间相互作用的结果,可为进一步研究提供参考。

Objective:To analyze the gene expression profile of knee joint synovial tissue in patients with osteoarthritis.Methods:The microarray data were selected from the common gene chip database,and the differentially expressed genes in synovial tissue of osteoarthritis patients and normal synovial tissue were screened by GEO2R,the Gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of the screened genes were carried out.The protein-protein interaction(PPI)network was constructed by STRING database and Cytoscape software,which presented the hub genes.Results:A total of two sets of osteoarthritis gene chip data from databases were included.131 common DEGs were screened out,including 98 up-regulated genes and 33 down-regulated genes.GO enrichment analysis revealed that DEGs were mainly enriched in cell adhesion,response to fibroblast growth factor stimulation,and intracellular receptor signaling pathways.KEGG pathway demonstrated the inflammatory signaling pathways involved in DEGs,such as mitogen-activated protein kinase(MAPK)signaling pathway,hypoxia-inducible factor-1(HIF-1)signaling pathway,phosphatidylinositol 3 kinase/protein kinase B(PI3K/Akt)signaling pathway.The PPI network showed 10 hub genes.Conclusion:Screening of differentially expressed genes by analyzing the expression profile of OA gene suggests that the pathogenesis of OA is not only related to cell proliferation,pathological angiogenesis and inflammatory stimulation,but also the result of the complex interactions between multiple signaling pathways and multiple targets,which can provide reference for further research.