股骨头坏死患者基因表达的转录组学高通量分析  

Gene expression profiling of patients with osteonecrosis of the femoral head:A transcriptomics high-throughput analysis

作　　者：白浩波 朱卫文[1] 路倩 张健[1] Bai Haobo;Zhu Weiwen;Lu Qian;Zhang Jian(Department of Orthopedics,The First Affiliated Hospital of Chongqing Medical University)

机构地区：[1]重庆医科大学附属第一医院关节外科

出　　处：《重庆医科大学学报》2019年第9期1149-1154,共6页Journal of Chongqing Medical University

基　　金：重庆市渝中区科委科学技术资助项目(编号:20150121)

摘　　要：目的:通过转录组方法,探索股骨头缺血性坏死发生发展过程中骨小梁改变的分子机制及预测股骨头坏死的诊断性生物标志物。方法:取4例股骨头坏死患者骨小梁组织(实验组)和4例股骨颈骨折患者骨小梁(对照组),通过转录组测序筛选差异基因;将筛选出的差异基因通过生物信息学软件分析,预测其可能参与的生物过程及信号通路。结果:高通量测序发现1527个差异基因(696个基因上调,831个基因下调),其中脂质运载蛋白2(lipocalin 2,LCN2)、过氧化物酶体增殖物激活受体-γ(peroxisome proliferators-activated receptorγ,PPARγ)在坏死患者骨小梁组织的表达明显降低。差异表达基因在基因本体论(gene ontology,GO)分析中主要富集于细胞外基质组织、细胞外结构组织等。差异基因在京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)分析主要富集于细胞外基质受体相互作用(extracellular matrix-receptor-interaction,ECM-receptor-interaction)、过氧化物酶体增殖物激活受体(peroxisome proliferators-activated receptors,PPARs)信号通路。结论:本研究发现脂质运载蛋白2通过调节脂质代谢和成骨分化影响股骨头坏死的产生。对探索股骨头缺血性坏死的分子机制及诊断性生物标志物提供了线索。Objective:To investigate the molecular mechanism of bone trabeculae in the development and progression of osteonecrosis of the femoral head(ONFH)and biomarkers for the diagnosis and prediction of ONFH.Methods:Bone trabecular tissue was collected from 4 patients with ONFH(experimental group)and 4 patients with femoral neck fracture(control group),and transcriptome sequencing was performed to screen out differentially expressed genes.These genes were analyzed using bioinformatics software to predict possible biological processes and signaling pathways involving these genes.Results:High-throughput sequencing identified1527 differentially expressed genes,with 696 upregulated genes and 831 downregulated genes,and there were significant reductions in the expression of lipocalin 2(LCN2)and peroxisome proliferator-activated receptor-γ(PPARγ)in bone trabecular tissue.The gene ontology analysis showed that the differentially expressed genes were mainly enriched in extracellular matrix(ECM)and extracellular structural tissue.The kyoto encyclopedia of genes and genome(KEGG)analysis showed that the differentially expressed genes were mainly enriched in ECM-receptor interaction and the PPARγsignaling pathway.Conclusion:This study shows that LCN2 affects the development of ONFH by regulating lipid metabolism and osteogenic differentiation,which provides a clue for exploring the molecular mechanism of ONFH and related diagnostic biomarkers.

关 键 词：转录组测序 骨小梁 股骨头缺血性坏死 脂代谢 脂质运载蛋白2 

分 类 号：R681.6[医药卫生—骨科学]