Liu Zhendong, Wang Hongbo, Cheng Xingbo, Zhang Jiangfen, Gao Yanzheng
Department of Surgery of Spine and Spinal Cord, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, 450003, Henan Province, China.
Department of Urology, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China.
Biochem Biophys Rep. 2023 Mar 5;34:101450. doi: 10.1016/j.bbrep.2023.101450. eCollection 2023 Jul.
Osteoarthritis (OA) is a common joint degenerative disease that can affect multiple joints. Genetic events may play an important regulatory role in the early stages of the disease, but the specific mechanisms have not yet been fully elucidated. The main purpose of this study was to screen for disease-causing hub genes and effective small molecule drugs to reveal the pathogenesis of OA and to develop novel drugs for treatment.
Two gene expression profile datasets, GSE55235 and GSE55457, were integrated and further analyzed. The consistently differentially expressed genes (DEGs) were identified, and functional annotation and pathway analysis of these genes were performed with GO and KEGG. A protein-protein interaction network (PPI) of the DEGs was generated using STRING, and potential small molecule drug screening was performed on the connectivity map (CMap).
A total of 158 consistently differentially expressed genes were identified from the two profile datasets. The functions of these DEGs are mainly related to the TNF signaling pathway, osteoclast differentiation, MAPK signaling pathway and so on. The PPI network contains 127 nodes and 1802 edges, and the ten hub genes were interleukin 6 (), vascular endothelial growth factor A ()and so on. 7 small molecule drugs were identified as potential interactors with these hubs.
This study explains the disorder of expression in the pathological process of OA at transcriptome, which will help to understand the pathogenesis of OA.
骨关节炎(OA)是一种常见的关节退行性疾病,可影响多个关节。遗传事件可能在该疾病的早期阶段发挥重要的调节作用,但具体机制尚未完全阐明。本研究的主要目的是筛选致病关键基因和有效的小分子药物,以揭示OA的发病机制并开发新型治疗药物。
整合并进一步分析了两个基因表达谱数据集GSE55235和GSE55457。鉴定出一致性差异表达基因(DEGs),并使用GO和KEGG对这些基因进行功能注释和通路分析。使用STRING生成DEGs的蛋白质-蛋白质相互作用网络(PPI),并在连接图谱(CMap)上进行潜在小分子药物筛选。
从两个图谱数据集中共鉴定出158个一致性差异表达基因。这些DEGs的功能主要与TNF信号通路、破骨细胞分化、MAPK信号通路等有关。PPI网络包含127个节点和1802条边,十个关键基因是白细胞介素6()、血管内皮生长因子A()等。7种小分子药物被鉴定为与这些关键基因的潜在相互作用物。
本研究从转录组水平解释了OA病理过程中的表达紊乱,这将有助于理解OA的发病机制。