骨质疏松症、膝骨关节炎与2型糖尿病的共病机制

Comorbidity mechanism of osteoporosis, knee osteoarthritis,and type 2 diabetes

目的依托疾病数据库探讨骨质疏松症、膝骨关节炎与2型糖尿病的共病机制。方法通过数据库(GeneCards、DrugBank、TTD、OMIM)、分析平台(VENNY、STRING、Metascape)及Cytoscape软件对骨质疏松症、膝骨关节炎及2型糖尿病的相关靶点进行分析筛选,并进行基因本体论(Gene Ontology,GO)生物过程以及京都基因和基因组途径百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果通过数据库筛选去重后获得与骨质疏松症、膝骨关节炎、2型糖尿病相关靶点分别为445、448、10035个,映射出交集靶点113个,以Degree≥70筛选出核心靶点9个:白介素-6(interleakin-6,IL-6)、肿瘤坏死因子(tumor necrosisfactor,TNF)、白介素-1β(interleakin-6,IL-1β)、胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)、血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)、白蛋白(albumin,ALB)、丝氨酸/苏氨酸激酶(threonine kinase1,AKT1)、分泌性磷蛋白1(secretory phosphoprotein 1,SPP1)、连环蛋白B1(catenin beta 1,CTNNB1)。将这9个核心靶点导入Metascape进行富集分析,获得9个GO生物过程富集结果,包括细胞发育、细胞增殖、神经炎症反应、胶质生成及脂质转运调节等生物过程,及4条KEGG通路,包括人巨细胞病毒感染、糖尿病并发症中的AGE-RAGE信号通路、焦点粘连、MAPK信号通路。结论骨质疏松症、膝骨关节炎与2型糖尿病3种疾病存在密切联系的分子机制,本研究为探索药物同时干预3种疾病的靶点机制提供参考价值。

Objective To explore the comorbidity mechanism of osteoporosis,knee osteoarthritis,and type 2 diabetes based on disease database.Methods The targets related to osteoporosis,knee osteoarthritis,and type 2 diabetes were analyzed and screened by databases(GeneCards,DrugBank,TTD,OMIM),analysis platforms(VENNY,STRING,Metascape),and Cytoscape software,and the screening results were analyzed by Go biological process enrichment analysis and KEGG pathway analysis.Results Totally 445,448,and 10035 targets related to osteoporosis,knee osteoarthritis,and type 2 diabetes were obtained after weight removal through database screening,113 intersection targets were mapped,and 9 core targets such as IL-6,TNF,IL-1β,IGF-1,VEGFA,ALB,AKT1,SPP1,CTNNB1 were screened with degree≥70.They were introduced into Metascape for enrichment analysis,and the enrichment results of 9 Go biological processes such as cell development,cell proliferation,neuroinflammatory reaction,gliogenesis,and lipid transport,and 4 KEGG pathways includes human cytomegalovirus infection,AGE-RAGE signaling pathway in diabetic complication,focal adhesion,MAPK signaling pathway were obtained.Conclusions Osteoporosis,knee osteoarthritis,and type 2 diabetes may have the comorbidity mechanisms.Results of this study may provides reference value for exploring the target mechanism of drug intervention in the three diseases.