Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Department of Rheumatology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710000, P.R. China.
Mol Med Rep. 2018 Mar;17(3):4467-4473. doi: 10.3892/mmr.2018.8429. Epub 2018 Jan 15.
Osteoarthritis (OA) has a high prevalence in female patients and sex may be a key factor affecting the progression of OA. The aim of the present study was to identify genetic signatures in the synovial membranes of female patients with OA and to elucidate the potential associated molecular mechanisms. The gene expression profiles of the GSE55457 and GSE55584 datasets were obtained from the Gene Expression Omnibus database. Data of two synovial membranes from normal female individuals (GSM1337306 and GSM1337310) and two synovial membranes from female patients affected by OA (GSM1337327 and GSM1337330) were obtained from the dataset GSE55457, and those of three synovial membranes from female patients affected by OA (GSM1339628, GSM1339629 and GSM1339632) were obtained from the dataset GSE55584. Differentially expressed genes (DEGs) were identified by using Morpheus software. Protein‑protein interaction (PPI) networks of the DEGs were constructed by using Cytoscape software. Subsequently, Gene Ontology (GO) function and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses of the top module of the PPI network were performed by using ClueGo. A total of 377 DEGs were identified in the synovial membranes of OA patients compared with those of normal individuals, including 164 upregulated and 213 downregulated genes. The top 10 hub genes were ubiquitin (UB)C, ribosomal protein (RP) L23A, mammalian target of rapamycin, heat shock protein 90 α family class A member 1, RPS28, RPL37A, RPS24, RPS4X, RPS18 and UBB. The results of the GO analysis indicated that the DEGs included in the top module of the PPI were mainly enriched in the terms 'nuclear‑transcribed mRNA catabolic process', 'nonsense mediated decay', and 'cytoplasmic translation and ribosomal small subunit biogenesis'. KEGG pathway analysis indicated that the DEGs included in the top one module were mainly enriched in the 'ribosome' pathway. The present study provides a systematic, molecular‑level understanding of the degeneration of the synovial membrane in the progression of OA in female patients. The hub genes and molecules associated with the synovial membrane may be used as biomarkers and therapeutic targets for the treatment of OA in female patients with OA.
骨关节炎(OA)在女性患者中患病率较高,性别可能是影响 OA 进展的关键因素。本研究旨在鉴定女性 OA 患者滑膜中的遗传特征,并阐明潜在的相关分子机制。从基因表达综合数据库中获得 GSE55457 和 GSE55584 数据集的基因表达谱。从数据集 GSE55457 中获得了 2 份来自正常女性个体的滑膜(GSM1337306 和 GSM1337310)和 2 份来自受 OA 影响的女性患者的滑膜(GSM1337327 和 GSM1337330)的数据,从数据集 GSE55584 中获得了 3 份来自受 OA 影响的女性患者的滑膜(GSM1339628、GSM1339629 和 GSM1339632)的数据。使用 Morpheus 软件鉴定差异表达基因(DEGs)。使用 Cytoscape 软件构建 DEGs 的蛋白质-蛋白质相互作用(PPI)网络。随后,使用 ClueGo 对 PPI 网络的顶级模块进行基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)途径富集分析。与正常个体相比,OA 患者滑膜中的 377 个 DEG 被鉴定出来,其中包括 164 个上调基因和 213 个下调基因。前 10 个枢纽基因是泛素(UB)C、核糖体蛋白(RP)L23A、哺乳动物雷帕霉素靶蛋白、热休克蛋白 90α 家族 A 成员 1、RPS28、RPL37A、RPS24、RPS4X、RPS18 和 UBB。GO 分析的结果表明,PPI 顶级模块中包含的 DEG 主要富集在“核转录 mRNA 分解代谢过程”、“无意义介导的衰变”和“细胞质翻译和核糖体小亚基生物发生”等术语中。KEGG 途径分析表明,顶级模块中包含的 DEG 主要富集在“核糖体”途径中。本研究为女性患者 OA 滑膜退行性变的进展提供了系统的、分子水平的认识。与滑膜相关的枢纽基因和分子可能被用作女性 OA 患者 OA 治疗的生物标志物和治疗靶点。