Wang Junjie, Fan Qin, Yu Tengbo, Zhang Yingze
Qingdao University, Qingdao, Shandong 266000, China.
Orthopaedic Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, China.
Curr Pharm Des. 2022;28(6):497-509. doi: 10.2174/1381612827666211104154459.
Osteoarthritis (OA) and rheumatoid arthritis (RA) are two common diseases that result in limb disability and a decrease in quality of life. The major symptoms of OA and RA are pain, swelling, stiffness, and malformation of joints, and each disease also has unique characteristics.
To compare the pathological mechanisms of OA and RA via weighted correlation network analysis (WGCNA) and immune infiltration analysis and find potential diagnostic and pharmaceutical targets for the treatment of OA and RA.
The gene expression profiles of ten OA and ten RA synovial tissue samples were downloaded from the Gene Expression Omnibus (GEO) database (GSE55235). After obtaining differentially expressed genes (DEGs) via GEO2R, WGCNA was conducted using an R package, and modules and genes that were highly correlated with OA and RA were identified. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network analyses were also conducted. Hub genes were identified using the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software. Immune infiltration analysis was conducted using the Perl program and CIBERSORT software.
Two hundred ninety-nine DEGs, 24 modules, 16 GO enrichment terms, 6 KEGG pathway enrichment terms, 10 hub genes (CXCL9, CXCL10, CXCR4, CD27, CD69, CD3D, IL7R, STAT1, RGS1, and ISG20), and 8 kinds of different infiltrating immune cells (plasma cells, CD8 T cells, activated memory CD4 T cells, T helper follicular cells, M1 macrophages, Tregs, resting mast cells, and neutrophils) were found to be involved in the different pathological mechanisms of OA and RA.
Inflammation-associated genes were the top differentially expressed hub genes between OA and RA, and their expression was downregulated in OA. Genes associated with lipid metabolism may have upregulated expression in OA. In addition, immune cells that participate in the adaptive immune response play an important role in RA. OA mainly involves immune cells that are associated with the innate immune response.
骨关节炎（OA）和类风湿关节炎（RA）是导致肢体残疾和生活质量下降的两种常见疾病。OA和RA的主要症状是疼痛、肿胀、僵硬和关节畸形，且每种疾病也有其独特特征。
通过加权基因共表达网络分析（WGCNA）和免疫浸润分析比较OA和RA的病理机制，并寻找治疗OA和RA的潜在诊断及药物靶点。
从基因表达综合数据库（GEO）（GSE55235）下载10例OA和10例RA滑膜组织样本的基因表达谱。通过GEO2R获得差异表达基因（DEG）后，使用R包进行WGCNA，并鉴定与OA和RA高度相关的模块和基因。还进行了基因本体论（GO）、京都基因与基因组百科全书（KEGG）富集分析以及蛋白质-蛋白质相互作用（PPI）网络分析。使用搜索相互作用基因的工具（STRING）和Cytoscape软件鉴定枢纽基因。使用Perl程序和CIBERSORT软件进行免疫浸润分析。
发现299个DEG、24个模块、16个GO富集项、6个KEGG通路富集项、10个枢纽基因（CXCL9、CXCL10、CXCR4、CD27、CD69、CD3D、IL7R、STAT1、RGS1和ISG20）以及8种不同的浸润免疫细胞（浆细胞、CD8 T细胞、活化记忆CD4 T细胞、滤泡辅助性T细胞、M1巨噬细胞、调节性T细胞、静息肥大细胞和中性粒细胞）参与了OA和RA的不同病理机制。
炎症相关基因是OA和RA之间差异表达最显著的枢纽基因，且其在OA中表达下调。与脂质代谢相关的基因在OA中可能表达上调。此外，参与适应性免疫反应的免疫细胞在RA中起重要作用。OA主要涉及与固有免疫反应相关的免疫细胞。
