Gao Xiang, Sun Yu, Li Xu
Department of Orthopedic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110000, P.R. China.
Exp Ther Med. 2019 Oct;18(4):2479-2490. doi: 10.3892/etm.2019.7848. Epub 2019 Aug 5.
Osteoarthritis (OA) is one of the most prevalent causes of joint disease. However, the pathological mechanisms of OA have remained to be completely elucidated, and further investigation into the underlying mechanisms of OA development and the identification of novel therapeutic targets are urgently required. In the present study, the dataset GSE114007 was downloaded from the Gene Expression Omnibus database. Based on weighted gene co-expression network analysis (WGCNA) and the identification of differentially expressed genes (DEGs), the microarray data were further analyzed to identify hub genes, key transcription factors (TFs) and pivotal signaling pathways involved in the pathogenesis of OA. A total of 1,898 genes were identified to be differentially expressed between OA samples and normal samples. Based on WGCNA, the present study identified 5 hub modules closely associated with OA, and the potential key TFs for hub modules were further explored based on CisTargetX. The results demonstrated that B-Cell Lymphoma 6, Myelin Gene Expression Factor 2, Activating Transcription Factor 3, CCAAT Enhancer Binding Protein γ, Nuclear Factor Interleukin-3-Regulated, FOS Like Antigen-2, FOS-Like Antigen-1, Fos Proto-Oncogene, JunD Proto-Oncogene, Transcription Factor CP2 Like 1, RELA proto-oncogene NF-kB subunit, SRY-box transcription factor 3, V-Ets Avian Erythroblastosis Virus E26 Oncogene Homolog 2, Interferon Regulatory Factor 4 and REL proto-oncogene, NF-kB subunit were the potential key TFs. In addition, osteoclast differentiation, FoxO, MAPK and PI3K/Akt signaling pathways were revealed to be imperative for the pathogenesis of OA, as these 4 pivotal signaling pathways were observed to be tightly linked through 4 key TFs Fos Proto-Oncogene, JUN, JunD Proto-Oncogene and MYC, and 4 DEGs Vascular Endothelial Growth Factor A, Growth Arrest and DNA Damage Inducible α, Growth Arrest and DNA Damage Inducible β and Cyclin D1. The present study identified a set of potential key genes and signaling pathways, and provided an important opportunity to advance the current understanding of OA.
骨关节炎（OA）是关节疾病最常见的病因之一。然而，OA的病理机制仍有待完全阐明，迫切需要进一步研究OA发生发展的潜在机制并确定新的治疗靶点。在本研究中，从基因表达综合数据库下载了数据集GSE114007。基于加权基因共表达网络分析（WGCNA）和差异表达基因（DEG）的鉴定，对微阵列数据进行进一步分析，以确定参与OA发病机制的枢纽基因、关键转录因子（TF）和关键信号通路。共鉴定出1898个基因在OA样本和正常样本之间存在差异表达。基于WGCNA，本研究确定了5个与OA密切相关的枢纽模块，并基于CisTargetX进一步探索了枢纽模块的潜在关键TF。结果表明，B细胞淋巴瘤6、髓磷脂基因表达因子2、激活转录因子3、CCAAT增强子结合蛋白γ、核因子白细胞介素-3调节因子、FOS样抗原-2、FOS样抗原-1、Fos原癌基因、JunD原癌基因、转录因子CP2样1、RELA原癌基因NF-κB亚基、SRY盒转录因子3、V-Ets禽成红细胞增多病毒E26癌基因同源物2、干扰素调节因子4和REL原癌基因NF-κB亚基是潜在的关键TF。此外，破骨细胞分化、FoxO、MAPK和PI3K/Akt信号通路被揭示对OA的发病机制至关重要，因为观察到这4条关键信号通路通过4个关键TF Fos原癌基因、JUN、JunD原癌基因和MYC以及4个DEG血管内皮生长因子A、生长停滞和DNA损伤诱导α、生长停滞和DNA损伤诱导β以及细胞周期蛋白D1紧密相连。本研究确定了一组潜在的关键基因和信号通路，为推进目前对OA的认识提供了重要契机。
