CD14和CSF1R作为诱导骨关节炎的发育性分子靶点。

IF 1.1 Q4 ONCOLOGY
Meiliang Zheng, Zheng Li, Yingfa Feng, Xiaoyu Zhang
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引用次数: 0

摘要

目的:骨关节炎(Osteoarthritis, OA)是一种以关节软骨损伤为主,累及整个关节组织的非炎性退行性关节疾病。然而,CD14和CSF1R与骨关节炎之间的关系尚不清楚。本研究旨在探讨CD14和CSF1R在骨关节炎中的重要作用,为骨关节炎的防治提供新的方向。方法:从GPL10558和GPL570生成的GEO数据库中下载骨关节炎数据集GSE46750和GSE82107。采用R包筛选差异表达基因(DEDs)。加权基因共表达网络分析(WGCNA)。构建蛋白-蛋白相互作用(PPI)网络,进行功能富集分析、基因集富集分析(GSEA)和比较毒物基因组学数据库(CTD)分析。targets.com可以筛选调控中心DEGs的mirna。结果:共鉴定出687个deg。根据基因本体(gene ontology, GO),它们主要集中在炎症反应、IL-17信号通路、类风湿关节炎、运动和对外部刺激反应的调节。富集项目类似于GO京都基因与基因组百科全书(KEGG)的DEGs富集项目。这些主要集中在运动、炎症反应、防御反应、含胶原的细胞外基质和受体调节剂活性。在metscape的富集项目中,GO具有炎症反应、SARS-CoV-2信号通路网络图谱、PIDIL8CXCR1通路、骨重塑和软骨内成骨调节等功能。通过PPI网络构建和分析得到20个核心基因。基因表达热图显示,核心基因(C1QC、CSF1R、CD14、TYROBP、HLA-DRA、C1QB、FCER1G、S100A9、HCLS1、WAS、BTK、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、急性髓性白血病和血小板减少症相关。结论:CD14和CSF1R在骨关节炎中高表达,可能成为骨关节炎的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CD14 and CSF1R as developmental molecular targets for the induction of osteoarthritis.

Objective: 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.

Method: 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.

Results: 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.

Conclusion: CD14 and CSF1R are highly expressed in osteoarthritis and may be therapeutic targets for osteoarthritis.

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来源期刊
自引率
0.00%
发文量
42
审稿时长
1 months
期刊介绍: The International Journal of Clinical and Experimental Pathology (IJCEP, ISSN 1936-2625) is a peer reviewed, open access online journal. It was founded in 2008 by an international group of academic pathologists and scientists who are devoted to the scientific exploration of human disease and the rapid dissemination of original data. Unlike most other open access online journals, IJCEP will keep all the traditional features of paper print that we are all familiar with, such as continuous volume and issue numbers, as well as continuous page numbers to keep our warm feelings towards an academic journal. Unlike most other open access online journals, IJCEP will keep all the traditional features of paper print that we are all familiar with, such as continuous volume and issue numbers, as well as continuous page numbers to keep our warm feelings towards an academic journal.
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