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miR-106a-5p/PTEN轴的失调与绝经后骨质疏松症的进展和诊断相关。

Dysregulation of miR-106a-5p/PTEN axis associated with progression and diagnostic of postmenopausal osteoporosis.

作者信息

Liu Xiangjie, Zhang Xiaogang, Cen Meini

机构信息

Department of Orthopedics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, China.

Department of Orthopedics, Hebei Yanda Hospital, Sanhe, 065201, China.

出版信息

J Orthop Surg Res. 2025 May 13;20(1):456. doi: 10.1186/s13018-025-05872-3.

Abstract

OBJECTIVE

Postmenopausal osteoporosis (PMOP) is a bone disorder in postmenopausal women and a significant risk factor for fragility fractures. This study aims to explore the role of miR-106a-5p in the pathogenesis of PMOP and its potential as a diagnostic biomarker.

METHODS

220 postmenopausal women were recruited. The levels of miR-106a-5p, PTEN, and osteogenic-related genes were quantified using qRT-PCR. The relative protein of PTEN was detected using Western blotting. ROC curve and Pearson correlation were employed to evaluate the diagnostic value and relationships between variables. To model iron accumulation, hFOB1.19 osteoblasts were treated with ferric ammonium citrate (FAC). Cell proliferation and apoptosis were assessed using the CCK-8 and flow cytometry. The target relationship was verified using dual-luciferase assays.

RESULTS

miR-106a-5p levels were reduced, while PTEN levels were increased in PMOP. miR-106a-5p was positively correlated with bone mineral density and negatively correlated with ferritin. In the FAC-treated cells, miR-106a-5p decreased, and PTEN increased. Dual-luciferase assays confirmed that miR-106a-5p targets PTEN. Successful transfection was confirmed by observing the corresponding changes in miR-106a-5p and PTEN expression. Up-regulated miR-106a-5p increased the PTEN protein level, mRNA expression of RUNX2, OPN, and OCN, promoted cell proliferation, and decreased cell apoptosis under iron accumulation conditions. These effects were reversed by the upregulation of PTEN.

CONCLUSION

miR-106a-5p has the potential to diagnose osteoporosis in postmenopausal women and is linked to ferritin levels. miR-106a-5p plays a protective role in PMOP by regulating PTEN under conditions of iron accumulation, suggesting its potential as a promising biomarker for PMOP.

摘要

目的

绝经后骨质疏松症(PMOP)是绝经后女性的一种骨骼疾病,也是脆性骨折的重要危险因素。本研究旨在探讨miR-106a-5p在PMOP发病机制中的作用及其作为诊断生物标志物的潜力。

方法

招募220名绝经后女性。使用qRT-PCR定量检测miR-106a-5p、PTEN和成骨相关基因的水平。使用蛋白质印迹法检测PTEN的相对蛋白水平。采用ROC曲线和Pearson相关性分析评估诊断价值及变量之间的关系。为模拟铁蓄积,用柠檬酸铁铵(FAC)处理人成骨细胞系hFOB1.19。使用CCK-8和流式细胞术评估细胞增殖和凋亡。使用双荧光素酶报告基因检测验证靶标关系。

结果

PMOP患者中miR-106a-5p水平降低,而PTEN水平升高。miR-106a-5p与骨密度呈正相关,与铁蛋白呈负相关。在FAC处理的细胞中,miR-106a-5p降低,PTEN升高。双荧光素酶报告基因检测证实miR-106a-5p靶向PTEN。通过观察miR-106a-5p和PTEN表达的相应变化证实转染成功。上调miR-106a-5p可增加PTEN蛋白水平、RUNX2、OPN和OCN的mRNA表达,促进细胞增殖,并在铁蓄积条件下减少细胞凋亡。PTEN的上调可逆转这些作用。

结论

miR-106a-5p具有诊断绝经后女性骨质疏松症的潜力,且与铁蛋白水平相关。miR-106a-5p在铁蓄积条件下通过调节PTEN在PMOP中发挥保护作用,表明其作为PMOP有前景的生物标志物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5766/12070524/f88776aa7b59/13018_2025_5872_Fig1_HTML.jpg

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