Huc-MSC-derived exosomes alleviates alcohol-induced osteonecrosis of the femoral head through targeting the miR-25-3p/GREM1 axis

IF 3.4 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Genomics Pub Date : 2025-01-16 DOI:10.1016/j.ygeno.2025.110996

Zhifang Tang , Xiaoyan Xu , Wei Shi , Xianzhen Ren , Huan Luo , Yongqing Xu , Chuan Li

{"title":"Huc-MSC-derived exosomes alleviates alcohol-induced osteonecrosis of the femoral head through targeting the miR-25-3p/GREM1 axis","authors":"Zhifang Tang , Xiaoyan Xu , Wei Shi , Xianzhen Ren , Huan Luo , Yongqing Xu , Chuan Li","doi":"10.1016/j.ygeno.2025.110996","DOIUrl":null,"url":null,"abstract":"<div><div>Osteonecrosis of the femoral head (ONFH) is a destructive bone disease, and overuse of alcohol is one of the major contributing factors. Although mesenchymal stem cells (MSCs) and their exosomes have been reported to attenuate ONFH, the potential mechanisms of alcohol-induced ONFH (AONFH) are unclear. Here, we isolated and identified human umbilical cord MSCs-derived exosomal (hucMSCs-exos) miR-25-3p. We observed that hucMSCs-exos transferred miR-25-3p into bone marrow stem cells (BMSCs). HucMSCs-exos miR-25-3p increased cell viability, osteogenic differentiation, and inhibited apoptosis of alcohol-treated BMSCs and AONFH rat model. Mechanically, hucMSCs-exos upregulated miR-25-3p expression in BMSCs by repressing miR-25-3p DNA methylation, and DNA methylation inhibitor 5-Aza-2-deoxycytidine (DAC) ameliorated AONFH. Besides, miR-25-3p suppressed gremlin 1 (GREM1) expression, and upregulation of GREM1 restored the inhibition of hucMSCs-exos on AONFH. Therefore, we determined that hucMSCs-exos miR-25-3p alleviated AONFH by inhibiting miR-25-3p DNA methylation and GREM1 expression, which may help identify novel biomarkers, diagnostic and therapeutic targets.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"117 2","pages":"Article 110996"},"PeriodicalIF":3.4000,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genomics","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0888754325000126","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Osteonecrosis of the femoral head (ONFH) is a destructive bone disease, and overuse of alcohol is one of the major contributing factors. Although mesenchymal stem cells (MSCs) and their exosomes have been reported to attenuate ONFH, the potential mechanisms of alcohol-induced ONFH (AONFH) are unclear. Here, we isolated and identified human umbilical cord MSCs-derived exosomal (hucMSCs-exos) miR-25-3p. We observed that hucMSCs-exos transferred miR-25-3p into bone marrow stem cells (BMSCs). HucMSCs-exos miR-25-3p increased cell viability, osteogenic differentiation, and inhibited apoptosis of alcohol-treated BMSCs and AONFH rat model. Mechanically, hucMSCs-exos upregulated miR-25-3p expression in BMSCs by repressing miR-25-3p DNA methylation, and DNA methylation inhibitor 5-Aza-2-deoxycytidine (DAC) ameliorated AONFH. Besides, miR-25-3p suppressed gremlin 1 (GREM1) expression, and upregulation of GREM1 restored the inhibition of hucMSCs-exos on AONFH. Therefore, we determined that hucMSCs-exos miR-25-3p alleviated AONFH by inhibiting miR-25-3p DNA methylation and GREM1 expression, which may help identify novel biomarkers, diagnostic and therapeutic targets.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

huc - msc衍生的外泌体通过靶向miR-25-3p/GREM1轴减轻酒精诱导的股骨头骨坏死。

股骨头骨坏死（ONFH）是一种破坏性的骨病，过度饮酒是其主要诱因之一。虽然间充质干细胞（MSCs）及其外泌体已被报道可减弱ONFH，但酒精诱导的ONFH （AONFH）的潜在机制尚不清楚。在这里，我们分离并鉴定了人脐带mscs衍生的外泌体（hucMSCs-exos） miR-25-3p。我们观察到humscs -exos将miR-25-3p转移到骨髓干细胞（BMSCs）中。HucMSCs-exos miR-25-3p增加酒精处理的BMSCs和AONFH大鼠模型的细胞活力，成骨分化，并抑制凋亡。机械地，hucMSCs-exos通过抑制miR-25-3p DNA甲基化上调BMSCs中miR-25-3p的表达，DNA甲基化抑制剂5- aza -2-脱氧胞苷（DAC）改善AONFH。此外，miR-25-3p抑制GREM1的表达，上调GREM1恢复了hucMSCs-exos对AONFH的抑制作用。因此，我们确定humscs -exos miR-25-3p通过抑制miR-25-3p DNA甲基化和GREM1表达来减轻AONFH，这可能有助于识别新的生物标志物、诊断和治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Genomics 生物-生物工程与应用微生物

CiteScore

9.60

自引率

2.30%

发文量

260

审稿时长

60 days

期刊介绍： Genomics is a forum for describing the development of genome-scale technologies and their application to all areas of biological investigation. As a journal that has evolved with the field that carries its name, Genomics focuses on the development and application of cutting-edge methods, addressing fundamental questions with potential interest to a wide audience. Our aim is to publish the highest quality research and to provide authors with rapid, fair and accurate review and publication of manuscripts falling within our scope.