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微小RNA-127-3p通过靶向囊泡相关膜蛋白2调节细胞分化来调控骨质疏松症进展。

miR-127-3p regulates osteoporosis progression by targeting VAMP2 to modulate cell differentiation.

作者信息

Chen Jing, Lei Jing, Wang Ganggang, Qin Huiling, Yang Li

机构信息

Department of Endocrinology and Metabolism, Shaoxing People's Hospital, Shaoxing, China.

The First Affiliated Hospital, Shaoxing University, Shaoxing, China.

出版信息

J Endocrinol. 2025 Aug 21;266(2). doi: 10.1530/JOE-25-0032. Print 2025 Aug 1.

Abstract

Osteoporosis (OP) is a systemic osteopathy characterized by a decrease in bone density and mass. Human bone mesenchymal stem cells (hBMSCs) exhibit multidirectional differentiation potential and play a critical role in bone metabolism. Herein, we investigated the diagnostic potential of miR-127-3p in OP and elucidated its regulatory role in hBMSCs, thereby providing novel insights into the diagnosis and progression prediction of OP. The relative expression of miR-127-3p was measured via RT-qPCR analysis. ROC curve and logistic analysis were applied to identify the diagnostic value of miR-127-3p for OP. The CCK8 assay and flow cytometry were used to assess cell viability and apoptosis. A luciferase reporter assay was performed to assess the interaction between VAMP2 and miR-127-3p. The bone differentiation markers RUNX2, OCN, and OPN were assayed using RT-qPCR and western blotting. We observed that the expression of miR-127-3p was reduced in patients with OP, allowing it to effectively distinguish these patients from healthy individuals. Transfection with miR-127-3p mimic inhibited hBMSC apoptosis, increased cell viability, and increased RUNX2, OCN, and OPN levels. Furthermore, miR-127-3p regulated hBMSCs via targeting VAMP2. Overexpression of VAMP2 reversed the effects of miR-127-3p on apoptosis, cell viability, and bone differentiation. In conclusion, these findings suggest that miR-127-3p may be a potential diagnostic tool for OP. In addition, miR-127-3p promotes hBMSC viability and differentiation through downregulating VAMP2; this decreases OP progression. Our findings will inform new ideas for the diagnosis and developmental prediction of OP.

摘要

骨质疏松症(OP)是一种以骨密度和骨量降低为特征的全身性骨病。人骨髓间充质干细胞(hBMSCs)具有多向分化潜能,在骨代谢中起关键作用。在此,我们研究了miR-127-3p在OP中的诊断潜力,并阐明了其在hBMSCs中的调控作用,从而为OP的诊断和病情进展预测提供了新的见解。通过RT-qPCR分析测量miR-127-3p的相对表达。应用ROC曲线和逻辑分析来确定miR-127-3p对OP的诊断价值。采用CCK8法和流式细胞术评估细胞活力和凋亡情况。进行荧光素酶报告基因检测以评估VAMP2与miR-127-3p之间的相互作用。使用RT-qPCR和蛋白质印迹法检测骨分化标志物RUNX2、OCN和OPN。我们观察到OP患者中miR-127-3p的表达降低,这使其能够有效地区分这些患者与健康个体。用miR-127-3p模拟物转染可抑制hBMSC凋亡,提高细胞活力,并增加RUNX2、OCN和OPN水平。此外,miR-127-3p通过靶向VAMP2调控hBMSCs。VAMP2的过表达逆转了miR-127-3p对凋亡、细胞活力和骨分化的影响。总之,这些发现表明miR-127-3p可能是OP的一种潜在诊断工具。此外,miR-127-3p通过下调VAMP2促进hBMSC活力和分化,从而减缓OP的进展。我们的研究结果将为OP的诊断和病情发展预测提供新思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a573/12372065/af14d2073130/JOE-25-0032fig1.jpg

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