摘要
目的基于基因芯片、高通量测序及免疫组织化学染色筛选验证骨关节炎(OA)进展相关基因,挖掘防治骨关节炎的新靶点。方法从基因表达数据库(GEO)获取骨关节炎数据集,筛选差异表达基因并进行基因本体论(GO)、京都基因和基因组数据库(KEGG)富集分析。通过构建差异表达基因蛋白质相互作用(PPI)网络,鉴定骨关节炎相关基因。分别以骨关节炎病人膝关节置换术后胫骨平台标本、创伤性截肢后胫骨平台为实验组、对照组,用免疫组织化学技术验证骨关节炎相关基因的表达。结果该研究筛选出骨关节炎上调基因950个、下调基因642个。骨关节炎相关基因富集在骨化、细胞分裂、蛋白质消化与吸收、PI3K-Akt信号通路及中性粒细胞外陷形成信号途径。根据PPI度值及聚类分析结果,获得了新型骨关节炎相关基因骨形态蛋白5(BMP5)、白细胞介素2受体亚基β(IL2RB)、白细胞介素(IL)-7、胎盘生长因子(PGF)、溶血磷脂酸受体3(LP⁃AR3)、白细胞介素5受体α亚基(IL5RA)和有丝分裂原激活蛋白激酶14(MAPK14)。免疫组织化学检测结果证实,BMP5、IL2RB、IL-7、PGF、LPAR3在OA组呈高表达(P<0.05);IL5RA和MAPK14在OA组呈低表达(P<0.05)。结论BMP5、IL2RB、IL-7、PGF、LPAR3表达上调与骨关节炎进展正相关,IL5RA、MAPK14表达上调则与骨关节炎进展负相关。
Objective To screen the genes related to the progression of osteoarthritis based on gene chip,high-throughput sequencing and immunohistochemical staining,and to provide new targets for the prevention and treatment of osteoarthritis.Methods The osteoarthritis data set was obtained from the Gene Expression Omnibus(GEO)database,and the differentially expressed genes were screened and analyzed by gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.Osteoarthritis-related genes were identified by constructing a differentially expressed gene protein-protein interaction(PPI)network.The tibial plateau specimens of osteoarthritis patients after total knee arthroplasty(TKA)and the tibial plateau after traumatic amputation were used as the experiment group and the control group,respectively.The expression of osteoarthritis-related genes was verified by immunohistochemistry.Results In this study,950 up-regulated genes and 642 down-regulated genes were screened out.Osteoarthritis-related genes were enriched in ossification,cell division,protein digestion and absorption,PI3K-Akt signaling pathway,and neutrophil exocytosis signaling pathway.Based on the degree values and clustering analysis results of the PPI network,bone morphogenetic protein 5(BMP5),interleukin-2 receptor subunit beta(IL2RB),interleukin-7(IL-7),placental growth factor(PGF),lysophosphatidic acid receptor 3(LPAR3),interleukin-5 receptor subunit alpha(IL5RA)and mitogen-activated protein kinase 14(MAPK14)were identified as the novel osteoarthritis-related genes.The results of immunohistochemistry showed that BMP5,IL2RB,IL-7,PGF,and LPAR3 were highly expressed in OA group while IL5RA and MAPK14 were lowly expressed in OA group(P<0.05).Conclusion The up-regulated expression of BMP5,IL2RB,IL-7,PGF and LPAR3 was positively correlated with the progression of osteoarthritis,while that of IL5RA and MAPK14 was negatively correlated with the progression of osteoarthritis.
作者
丘立标
李建棣
高莉
谢璐茜
俸浩翔
黄婉英
杨霞
陈罡
Qiu Libiao;Li Jiandi;Gao Li;Xie Luxi;Feng Haoxiang;Huang Wanyin;Yang Xia;Cheng Gang(Department of Pathology,The First Affiliated Hospital of Guangxi Medical University,Nanning,Guangxi Zhuang Autonomous Region 530022,China;Department of Pathology,Liuzhou People's Hospital,Liuzhou,Guangxi Zhuang Autonomous Region 545006,China)
出处
《安徽医药》
2026年第5期942-947,I0005,I0006,共8页
Anhui Medical and Pharmaceutical Journal
