Integrative analyses of genetic characteristics associated with skeletal endothelial cells

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-04-19 DOI:10.1590/1414-431X2024e13339

Zhanhui Wang, B. Hu, Xiaoming Chen, Zheng Zhang, Lu Liu, Nan Li, Chun Liang

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Abstract

Abstract The osseous vascular endothelium encompasses a vast intricate framework that regulates bone remodeling. Osteoporosis, an age-associated systemic bone disease, is characterized by the degeneration of the vascular architecture. Nevertheless, the precise mechanisms underpinning the metamorphosis of endothelial cells (ECs) with advancing age remain predominantly enigmatic. In this study, we conducted a systematic analysis of differentially expressed genes (DEGs) and the associated pathways in juvenile and mature femoral ECs, utilizing data sourced from the Gene Expression Omnibus (GEO) repositories (GSE148804) and employing bioinformatics tools. Through this approach, we successfully discerned six pivotal genes, namely Adamts1, Adamts2, Adamts4, Adamts14, Col5a1, and Col5a2. Subsequently, we constructed a miRNA-mRNA network based on miRNAs displaying differential expression between CD31hiEMCNhi and CD31lowEMCNlow ECs, utilizing online repositories for prediction. The expression of miR-466i-3p and miR-466i-5p in bone marrow ECs exhibited an inverse correlation with age. Our in vivo experiments additionally unveiled miR-466i-5p as a pivotal regulator in osseous ECs and a promising therapeutic target for age-related osteoporosis.

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骨骼内皮细胞相关遗传特征的综合分析

摘要骨血管内皮包括一个庞大而复杂的框架，它调节着骨的重塑。骨质疏松症是一种与年龄相关的全身性骨病，其特点是血管结构退化。然而，随着年龄的增长，内皮细胞（ECs）蜕变的确切机制仍然是个谜。在这项研究中，我们利用基因表达总库（GEO）资源库（GSE148804）中的数据，并采用生物信息学工具，对幼年和成熟股骨头内皮细胞中的差异表达基因（DEGs）及其相关通路进行了系统分析。通过这种方法，我们成功地发现了六个关键基因，即 Adamts1、Adamts2、Adamts4、Adamts14、Col5a1 和 Col5a2。随后，我们根据在 CD31hiEMCNhi 和 CD31lowEMCNlow ECs 之间有差异表达的 miRNA，利用在线资源库进行预测，构建了 miRNA-mRNA 网络。骨髓EC中miR-466i-3p和miR-466i-5p的表达与年龄呈反相关。我们的体内实验进一步揭示了miR-466i-5p是骨EC的关键调节因子，也是治疗年龄相关性骨质疏松症的一个有希望的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.