Liang Fan, Peng Le, Ma Yong-Gang, Hu Wei, Zhang Wei-Bing, Deng Ming, Li Ya-Ming
Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Exp Ther Med. 2022 Jan;23(1):6. doi: 10.3892/etm.2021.10928. Epub 2021 Oct 27.
Osteoarthritis (OA) is the most prevalent chronic degenerative disease that affects the health of the elderly. The present study aimed to identify significant genes involved in OA via bioinformatics analysis. A gene expression dataset (GSE104793) was downloaded from the Gene Expression Omnibus. Bioinformatics analysis was then performed in order to identify differentially expressed genes (DEGs) between untreated chondrocytes and chondrocytes cultured with interleukin-1β (IL-1β) for 24 h. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using Metascape. A protein-protein interaction network of DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes. Gene set enrichment analysis (GSEA) was performed using GSEA software. Furthermore, chondrocytes were extracted and treated with IL-1β (10 ng/ml) for 24 h, and reverse-transcription quantitative PCR was used to confirm differential expression of hub genes. Patient samples were also collected to verify the bioinformatic analysis results. Based on the cut-off criteria used for determination of the DEGs, a total of 844 DEGs, including 498 upregulated and 346 downregulated DEGs, were identified. The DEGs were mainly enriched in the GO terms and KEGG pathways 'inflammatory response', 'negative regulation of cell proliferation', 'ossification', 'taxis', 'blood vessel morphogenesis', 'extracellular structure organization', 'mitotic cell cycle process' and 'TNF signaling pathway'. The majority of the PCR results, namely the differential expression of kininogen 2, complement C3, cyclin B1, cell division cycle 20, cyclin A2, 1-phosphatidylinositol 4-kinase, BUB1 mitotic checkpoint serine/threonine kinase, kinesin family member 11, cyclin B2 and BUB1 mitotic checkpoint serine/threonine kinase B were consistent with the bioinformatics results. Collectively, the present observations provided a regulation network of IL-1β-stimulated chondrocytes, which may provide potential targets of OA therapy.
骨关节炎(OA)是影响老年人健康的最常见慢性退行性疾病。本研究旨在通过生物信息学分析确定参与OA的重要基因。从基因表达综合数据库下载了一个基因表达数据集(GSE104793)。然后进行生物信息学分析,以鉴定未处理的软骨细胞与用白细胞介素-1β(IL-1β)培养24小时的软骨细胞之间的差异表达基因(DEG)。使用Metascape进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。使用检索相互作用基因的搜索工具构建DEG的蛋白质-蛋白质相互作用网络。使用GSEA软件进行基因集富集分析(GSEA)。此外,提取软骨细胞并用IL-1β(10 ng/ml)处理24小时,并使用逆转录定量PCR来确认枢纽基因的差异表达。还收集了患者样本以验证生物信息学分析结果。基于用于确定DEG的截断标准,共鉴定出844个DEG,包括498个上调的DEG和346个下调的DEG。这些DEG主要富集在GO术语和KEGG通路的“炎症反应”、“细胞增殖的负调控”、“骨化”、“趋化性”、“血管形态发生”、“细胞外结构组织”、“有丝分裂细胞周期过程”和“TNF信号通路”中。大多数PCR结果,即激肽原2、补体C3、细胞周期蛋白B1、细胞分裂周期20、细胞周期蛋白A2、1-磷脂酰肌醇4-激酶、BUB-1有丝分裂检查点丝氨酸/苏氨酸激酶、驱动蛋白家族成员11、细胞周期蛋白B2和BUB-1有丝分裂检查点丝氨酸/苏氨酸激酶B的差异表达与生物信息学结果一致。总体而言,本研究结果提供了IL-1β刺激的软骨细胞的调控网络,这可能为OA治疗提供潜在靶点。