摘要
背景:骨关节炎是老年人中常见的慢性疾病之一,目前还没有有效的治疗方法。目的:鉴定骨关节炎滑膜组织中的差异表达基因和相关信号通路,阐明骨关节炎的发病机制并寻找有效的药物靶点。方法:①从GEO数据库中收集10个相关数据集,包括120个骨关节炎患者滑膜组织样本和85个正常人滑膜组织样本,鉴定出差异表达基因;②对这些差异表达基因进行GO功能富集分析和KEGG通路富集分析,使用Cytoscape软件构建差异表达基因的蛋白质-蛋白质相互作用网络,并进行了模块分析,筛选关键基因;③通过Drugbank数据库筛选获准的用于治疗骨关节炎的药物,Drug Gene Interaction数据库挖掘这些药物的靶基因。结果与结论:①文章总共鉴定出25个差异表达基因,包括20个上调的差异表达基因(SPP1、基质金属蛋白酶1及基质金属蛋白酶9等)和5个下调的差异表达基因(APOD、FKBP5及ZBTB16等);②GO功能富集分析结果表明,这些差异表达基因主要参与细胞外基质的代谢(例如胶原分解代谢过程、细胞外基质分解、胶原代谢过程、细胞外结构组织和蛋白质代谢过程);③KEGG富集分析结果表明,差异表达基因主要富集在“白细胞介素17信号通路”和“类风湿关节炎”;④通过Drugbank数据库和Drug Gene Interaction数据库共挖掘出50种获得批准的治疗骨关节炎药物及对应的209个靶基因,SPP1、基质金属蛋白酶1和基质金属蛋白酶9是治疗骨关节炎药物硫酸软骨素、曲安西龙、塞来昔布和葡萄糖胺的靶基因和差异表达基因的交集基因;⑤结果证实,骨关节炎发病可能与滑膜内特异表达的基因诱导细胞外基质的降解有关,SPP1、基质金属蛋白酶1和基质金属蛋白酶9可能是用于治疗骨关节炎的有效分子靶标。
BACKGROUND:Osteoarthritis is one of the most common chronic diseases in the old adults,and currently there is no effective treatment.OBJECTIVE:To identify differentially expressed genes and related signaling pathways in synovial tissue of osteoarthritis,elucidate the pathogenesis of osteoarthritis and seek for effective drug targets.METHODS:Ten related data sets were collected from GEO database,including 120 synovial tissue samples from patients with osteoarthritis and 85 samples from normal subjects,and the differentially expressed genes were identified.Genetic ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on these differentially expressed genes.The protein-protein interaction network of differentially expressed genes was constructed using Cytoscape software,and module analysis was performed to screen key genes.Through the Drugbank database,approved drugs for osteoarthritis were screened,and the target genes for these drugs were mined in the Drug Gene Interaction database.RESULTS AND CONCLUSION:A total of 25 differentially expressed genes were identified,including 20 up-regulated differentially expressed genes(SPP1,matrix metalloproteinase 1,matrix metalloproteinase 9,etc.)and 5 down-regulated differentially expressed genes(APOD,FKBP5,ZBTB16,etc.).GO functional enrichment analysis showed that these differentially expressed genes were mainly involved in the metabolism of extracellular matrix(e.g.,collagen catabolism,extracellular matrix catabolism,collagen metabolism,extracellular structure,and tissue and protein metabolism).KEGG enrichment analysis showed that the differentially expressed genes were mainly concentrated in the“interleukin-17 signaling pathway”and“rheumatoid arthritis.”Through the Drugbank database and the Drug Gene Interaction database,a total of 50 approved osteoarthritis drugs and their corresponding 209 target genes were identified.SPP1,matrix metalloproteinase 1 and matrix metalloproteinase 9 were the intersection genes of the differentially expressed genes and the target genes of the osteoarthritis drug chondroitin sulfate,triamcinolone and celecoxib,and glucosamine.To conclude,the pathogenesis of osteoarthritis may be related to the degradation of extracellular matrix induced by the genes expressed in the synovial membrane.SPP1,matrix metalloproteinase 1 and matrix metalloproteinase 9 may be effective molecular targets for the treatment of osteoarthritis.
作者
刘金富
曾平
农焦
范思奇
冯程钦
黄佳兴
Liu Jinfu;Zeng Ping;Nong Jiao;Fan Siqi;Feng Chengqin;Huang Jiaxing(Graduate School of Guangxi University of Chinese Medicine,Nanning 530299,Guangxi Zhuang Autonomous Region,China;The First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,Guangxi Zhuang Autonomous Region,China)
出处
《中国组织工程研究》
CAS
北大核心
2021年第23期3690-3696,共7页
Chinese Journal of Tissue Engineering Research
基金
国家自然科学基金项目(81960876),项目负责人:曾平
广西地区自然科学基金项目(2017GXNSFAA198296),项目负责人:曾平
广西中医药大学第一附属医院院级项目(2017ZD002),项目负责人:曾平。
关键词
软组织
滑膜
骨关节炎
芯片
基因
信号通路
细胞
靶点
soft tissue
synovium
osteoarthritis
microarray chip
gene
signaling pathway
cell
target
