骨质疏松性骨折中的miRNA-mRNA网络揭示了hsa-miR-32-3p/TNFSF11轴的功能机制。

MiRNA-mRNA network in osteoporotic fractures proposes the functional mechanism of hsa-miR-32-3p/TNFSF11 axis.

作者信息

Zeng Yukai, Zhao Bo, Gong Jiawei, Zhang Qingfeng, Yang Fei

机构信息

School of Biomedical Engineering, Capital Medical University, Beijing, 100069, China.

Department of Orthopedic Surgery, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, China.

出版信息

J Orthop Surg Res. 2025 Apr 29;20(1):426. doi: 10.1186/s13018-025-05836-7.

DOI:10.1186/s13018-025-05836-7

PMID:40301936

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12039004/

Abstract

BACKGROUND AND AIMS

This study aimed to construct a miRNA-mRNA network in OF and explored the effect of the hsa-miR-32-3p/TNFSF11 axis on osteoclast function.

METHODS

GSE70318 and GSE74209 datasets were used to filter the differentially expressed miRNAs in OF. Then, the targets of these miRNAs intersected with the disease genes of OF. The target genes were annotated using GO terms and KEGG pathway enrichment analysis. The network for miRNA-gene-top 30 GO terms/top 20 pathways was drawn. Sankey diagrams were drawn for Parathyroid hormone synthesis, secretion, and action pathway (hsa04928) and ossification (GO:0001503) related to osteoporotic fracture. The hsa-miR-32-3p/TNFSF11 axis was selected for expression and functional verification.

RESULTS

A total of 21 differentially expressed miRNAs in OF were obtained by analyzing GSE70318 and GSE74209 datasets. A total of 36 genes were related to OF among the miRNA-targets. The genes were enriched in GO terms and KEGG pathways related to OF. Parathyroid hormone synthesis, secretion, and action pathway (hsa04928) and ossification proposed that the hsa-miR-32-3p/TNFSF11 axis may be involved in OF. The expression level of hsa-miR-32-3p was decreased in patients with low bone mineral density (BMD) and fracture, while the expression level of TNFSF11 mRNA was increased. Hsa-miR-32-3p complementarily bound with TNFSF11. Hsa-miR-32-3p inhibited osteoclast activation, while TNFSF11 promoted osteoclast activation.

CONCLUSIONS

The miRNA-mRNA network in OF proposed the TNFSF11 as a downstream target of hsa-miR-32-3p. The hsa-miR-32-3p/TNFSF11 axis was involved in the regulation of osteoclast activity.

CLINICAL TRIAL NUMBER

Not applicable.

摘要

背景与目的

本研究旨在构建骨质疏松症（OF）中的miRNA-mRNA网络，并探究hsa-miR-32-3p/TNFSF11轴对破骨细胞功能的影响。

方法

利用GSE70318和GSE74209数据集筛选OF中差异表达的miRNA。然后，将这些miRNA的靶标与OF的疾病基因进行交集分析。使用GO术语和KEGG通路富集分析对靶基因进行注释。绘制miRNA-基因-前30个GO术语/前20条通路的网络。绘制与骨质疏松性骨折相关的甲状旁腺激素合成、分泌及作用通路（hsa04928）和骨化（GO:0001503）的桑基图。选择hsa-miR-32-3p/TNFSF11轴进行表达和功能验证。

结果

通过分析GSE70318和GSE74209数据集，共获得OF中21个差异表达的miRNA。miRNA靶标中共有36个基因与OF相关。这些基因在与OF相关的GO术语和KEGG通路中富集。甲状旁腺激素合成、分泌及作用通路（hsa04928）和骨化表明hsa-miR-32-3p/TNFSF11轴可能参与OF。低骨密度（BMD）和骨折患者中hsa-miR-32-3p的表达水平降低，而TNFSF11 mRNA的表达水平升高。Hsa-miR-32-3p与TNFSF11互补结合。Hsa-miR-32-3p抑制破骨细胞活化，而TNFSF11促进破骨细胞活化。