MicroRNA-584-5p/RUNX family transcription factor 2 axis mediates hypoxia-induced osteogenic differentiation of periosteal stem cells.

IF 3.6 3区医学 Q3 CELL & TISSUE ENGINEERING

World journal of stem cells Pub Date : 2023-10-26 DOI:10.4252/wjsc.v15.i10.979

Jia-Jia Lu, Xiao-Jian Shi, Qiang Fu, Yong-Chuan Li, Lei Zhu, Nan Lu

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引用次数: 0

Abstract

Background: The hypoxic environment during bone healing is important in regulating the differentiation of periosteal stem cells (PSCs) into osteoblasts or chondrocytes; however, the underlying mechanisms remain unclear.

Aim: To determine the effect of hypoxia on PSCs, and the expression of microRNA-584-5p (miR-584-5p) and RUNX family transcription factor 2 (RUNX2) in PSCs was modulated to explore the impact of the miR-584-5p/RUNX2 axis on hypoxia-induced osteogenic differentiation of PSCs.

Methods: In this study, we isolated primary mouse PSCs and stimulated them with hypoxia, and the characteristics and functional genes related to PSC osteogenic differentiation were assessed. Constructs expressing miR-584-5p and RUNX2 were established to determine PSC osteogenic differentiation.

Results: Hypoxic stimulation induced PSC osteogenic differentiation and significantly increased calcified nodules, intracellular calcium ion levels, and alkaline phosphatase (ALP) activity in PSCs. Osteogenic differentiation-related factors such as RUNX2, bone morphogenetic protein 2, hypoxia-inducible factor 1-alpha, and ALP were upregulated; in contrast, miR-584-5p was downregulated in these cells. Furthermore, upregulation of miR-584-5p significantly inhibited RUNX2 expression and hypoxia-induced PSC osteogenic differentiation. RUNX2 was the target gene of miR-584-5p, antagonizing miR-584-5p inhibition in hypoxia-induced PSC osteogenic differentiation.

Conclusion: Our study showed that the interaction of miR-584-5p and RUNX2 could mediate PSC osteogenic differentiation induced by hypoxia.

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MicroRNA-584-5p/RUNX家族转录因子2轴介导缺氧诱导骨膜干细胞成骨分化。

背景:骨愈合过程中的缺氧环境对骨膜干细胞(PSCs)向成骨细胞或软骨细胞的分化具有重要的调节作用;然而，潜在的机制仍不清楚。目的:研究缺氧对PSCs的影响，通过调控microRNA-584-5p (miR-584-5p)和RUNX家族转录因子2 (RUNX2)在PSCs中的表达，探讨miR-584-5p/RUNX2轴对缺氧诱导的PSCs成骨分化的影响。方法:本研究通过分离小鼠原代PSCs并进行缺氧刺激，评估其成骨分化特征及相关功能基因。构建表达miR-584-5p和RUNX2的构建体来检测PSC成骨分化。结果:缺氧刺激诱导PSC成骨分化，显著增加PSC钙化结节、细胞内钙离子水平和碱性磷酸酶(ALP)活性。RUNX2、骨形态发生蛋白2、缺氧诱导因子1- α、ALP等成骨分化相关因子上调;相反，miR-584-5p在这些细胞中下调。此外，miR-584-5p的上调显著抑制RUNX2表达和缺氧诱导的PSC成骨分化。RUNX2是miR-584-5p的靶基因，可拮抗miR-584-5p在缺氧诱导的PSC成骨分化中的抑制作用。结论:我们的研究表明miR-584-5p与RUNX2的相互作用可介导缺氧诱导的PSC成骨分化。

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

World journal of stem cells Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

7.80

自引率

4.90%

发文量

750

期刊介绍： The World Journal of Stem Cells (WJSC) is a leading academic journal devoted to reporting the latest, cutting-edge research progress and findings of basic research and clinical practice in the field of stem cells. It was launched on December 31, 2009 and is published monthly (12 issues annually) by BPG, the world''s leading professional clinical medical journal publishing company.