Zheng Meiliang, Li Zheng, Feng Yingfa, Zhang Xiaoyu
Department of Orthopedics, The Second Central Hospital of Baoding No. 57 Fanyang Zhong Road, Zhuozhou 072750, Hebei, China.
Department of Orthopedics, The Fourth Hospital of Hebei Medical University No. 12 Jiankang Road, Shijiazhuang 050011, Hebei, China.
Int J Clin Exp Pathol. 2023 Aug 15;16(8):184-198. eCollection 2023.
Osteoarthritis (OA) is a non-inflammatory degenerative joint disease that mainly involves articular cartilage damage and involves the whole joint tissue. However, the relationship between CD14 and CSF1R and osteoarthritis remains unclear. The aim of this study was to explore the important role of CD14 and CSF1R in osteoarthritis and provide a new direction for its prevention and treatment.
The osteoarthritis datasets GSE46750 and GSE82107 were downloaded from gene expression omnibus (GEO) database generated by GPL10558 and GPL570. R package limma was used to screen differentially expressed genes (DEDs). Weighted gene co-expression network analysis (WGCNA) was performed. The construction and analysis of a protein-protein interaction (PPI) network, functional enrichment analysis, gene set enrichment analysis (GSEA), and comparative toxicogenomics database (CTD) analysis were performed. TargetScan screened miRNAs that regulated central DEGs.
687 DEGs were identified. According to gene ontology (GO), they were mainly concentrated in inflammatory response, IL-17 signaling pathway, rheumatoid arthritis, exercise, and regulation of response to external stimuli. The enrichment items are similar to the GO Kyoto Encyclopedia of Gene and Genome (KEGG) enrichment items of DEGs. These were mainly concentrated in exercise, inflammatory response, defense response, collagen containing extracellular matrix, and receptor regulator activity. In an enrichment project of Metascape, GO had inflammatory response, SARS-CoV-2 signal pathway network map, PIDIL8CXCR1 pathway, regulation of bone remodeling and endochondral ossification. 20 core genes were obtained by PPI network construction and analysis. Gene expression heat map showed that core genes (C1QC, CSF1R, CD14, TYROBP, HLA-DRA, C1QB, FCER1G, S100A9, HCLS1, WAS, BTK, TREM1) were highly expressed in osteoarthritis synovial tissues and were low in normal synovial tissues. CTD analysis showed that twelve genes (C1QC, CSF1R, CD14, TYROBP, HLA-DRA, C1QB, FCER1G, S100A9, HCLS1, WAS, BTK, TREM1) were found to be associated with inflammation, necrosis, gout, acute myeloid leukemia and thrombocytopenia.
CD14 and CSF1R are highly expressed in osteoarthritis and may be therapeutic targets for osteoarthritis.
骨关节炎（OA）是一种非炎症性退行性关节疾病，主要涉及关节软骨损伤并累及整个关节组织。然而，CD14和集落刺激因子1受体（CSF1R）与骨关节炎之间的关系仍不清楚。本研究的目的是探讨CD14和CSF1R在骨关节炎中的重要作用，并为其防治提供新方向。
从基因表达综合数据库（GEO）中下载由GPL10558和GPL570生成的骨关节炎数据集GSE46750和GSE82107。使用R包limma筛选差异表达基因（DED）。进行加权基因共表达网络分析（WGCNA）。构建并分析蛋白质-蛋白质相互作用（PPI）网络、功能富集分析、基因集富集分析（GSEA）以及比较毒理基因组学数据库（CTD）分析。TargetScan筛选调控核心差异表达基因的微小RNA（miRNA）。
共鉴定出687个差异表达基因。根据基因本体论（GO），它们主要集中在炎症反应、白细胞介素-17信号通路、类风湿关节炎、运动以及对外界刺激反应的调控。这些富集条目与差异表达基因的GO京都基因与基因组百科全书（KEGG）富集条目相似。这些主要集中在运动、炎症反应、防御反应、含胶原细胞外基质以及受体调节活性。在Metascape的一个富集项目中，GO有炎症反应、严重急性呼吸综合征冠状病毒2信号通路网络图、PIDIL8CXCR1通路、骨重塑和软骨内成骨的调控。通过PPI网络构建和分析获得了20个核心基因。基因表达热图显示，核心基因（补体成分1q亚成分C（C1QC）、集落刺激因子1受体（CSF1R）、CD14、酪氨酸蛋白激酶结合蛋白（TYROBP）、人类白细胞抗原DRα（HLA-DRA）、补体成分1q亚成分B（C1QB）、高亲和力免疫球蛋白γ链受体Ⅰ（FCER1G）、钙结合蛋白S100A9（S100A9）、造血细胞特异性Lyn底物1（HCLS1）、Wiskott-Aldrich综合征蛋白（WAS）、布鲁顿酪氨酸激酶（BTK）、触发受体表达于髓系细胞1（TREM1））在骨关节炎滑膜组织中高表达，在正常滑膜组织中低表达。CTD分析显示，发现12个基因（C1QC、CSF1R、CD14、TYROBP、HLA-DRA、C1QB、FCER1G、S100A9、HCLS1、WAS、BTK、TREM1）与炎症、坏死、痛风、急性髓系白血病和血小板减少症有关。
CD14和CSF1R在骨关节炎中高表达，可能是骨关节炎的治疗靶点。
