Liu Guoqiang, He Guisong, Zhang Jie, Zhang Zhongmin, Wang Liang
Department of Orthopedics, Academy of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.
Department of Orthopedics, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Front Immunol. 2022 May 26;13:893301. doi: 10.3389/fimmu.2022.893301. eCollection 2022.
Synovial inflammation of joint tissue is the most important cause of tissue damage, joint destruction, and disability and is associated with higher morbidity or mortality. Therefore, this study aims to identify key genes in osteoarthritis synovitis tissue to increase our understanding of the underlying mechanisms of osteoarthritis and identify new therapeutic targets. Five GEO datasets with a total of 41 normal synovial membrane tissues and 45 osteoarthritis synovial membrane samples were used for analysis, and seven common differential genes were identified. The classification model constructed by LASSO analysis showed that six genes including CDKN1A, FOSB, STMN2, SLC2A3, TAC, and SCRG1 can be used as biomarkers of osteoarthritis, and the SCRG1 gene shows importance in osteoarthritis. Furthermore, drug database enrichment found that these six DEGs may be the drug targets of synovitis in osteoarthritis, and Valproic Acid CTD 00006977 may be a potential targeted therapeutic drug of SCRG1. Spearman correlation analysis was performed on the SCRG1 gene, and 27 genes with consistent expression were obtained. Functional analysis showed that 27 genes were mainly involved in metabolism, complement, antigen presentation, apoptosis, and regulation of immune pathways. The co-regulatory network of TFs-miRNA suggested that the SCRG1 gene may be regulated by hsa-miR-363-3p miRNA. In conclusion, SCRG1, as a diagnostic marker of osteoarthritis, co-regulates immune-related pathways through the interaction of related proteins, playing an important role in the occurrence and development of osteoarthritis, which may be a novel drug target.
关节组织的滑膜炎症是组织损伤、关节破坏和残疾的最重要原因,并且与较高的发病率或死亡率相关。因此,本研究旨在确定骨关节炎滑膜炎组织中的关键基因,以加深我们对骨关节炎潜在机制的理解,并确定新的治疗靶点。使用五个GEO数据集,共41个正常滑膜组织和45个骨关节炎滑膜样本进行分析,鉴定出七个常见的差异基因。通过LASSO分析构建的分类模型表明,包括CDKN1A、FOSB、STMN2、SLC2A3、TAC和SCRG1在内的六个基因可作为骨关节炎的生物标志物,且SCRG1基因在骨关节炎中显示出重要性。此外,药物数据库富集发现这六个差异表达基因可能是骨关节炎滑膜炎的药物靶点,丙戊酸CTD 00006977可能是SCRG1的潜在靶向治疗药物。对SCRG1基因进行Spearman相关性分析,获得27个表达一致的基因。功能分析表明,27个基因主要参与代谢、补体、抗原呈递、凋亡和免疫途径的调节。转录因子- microRNA的共调控网络表明,SCRG1基因可能受hsa-miR-363-3p microRNA调控。总之,SCRG1作为骨关节炎的诊断标志物,通过相关蛋白的相互作用共同调节免疫相关途径,在骨关节炎的发生发展中起重要作用,可能是一种新型药物靶点。