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微小RNA-210通过促进血管内皮生长因子(VEGF)表达和成骨细胞分化参与绝经后骨质疏松症的调控。

MicroRNA-210 is involved in the regulation of postmenopausal osteoporosis through promotion of VEGF expression and osteoblast differentiation.

作者信息

Liu Xiao-Dong, Cai Feng, Liu Liang, Zhang Yan, Yang An-Li

出版信息

Biol Chem. 2015 Apr;396(4):339-47. doi: 10.1515/hsz-2014-0268.

Abstract

MicroRNAs (miRNAs) are small non-protein-codingRNAs that function as negative gene expression regulators. miRNA-210 (miR-210) has recently been recognized in the pathogenesis of osteonecrosis associated with angiogenesis. Herein we aimed to explore the clinical significance of miR-210 treatment for postmenopausal osteoporosis. The expression of miR-210 was detected in bone marrow mesenchymal stem cells (BMSCs) in vitro and miR-210 significantly promoted the expression of vascular edothelial growth factor (VEGF) in BMSCs in a time-dependent manner (p<0.05). And miR-210 suppressed PPARγ expression but increased the expression of ALP and osterix, demonstrating that miR-210 inhibited adipocyte differentiation and promoted osteoblast differentiation of BMSCs in vitro. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and VEGF in 17β-estradiol (E2) treated osteoblasts were significantly increased in a dose- and time-dependent manner (p<0.05). And E2 inducted the VEGF expression through the PI3K/AKT signaling pathway in osteoblasts. Taken together, these data implied that miR-210 played an important role in ameliorating the estrogen deficiency caused-postmenopausal osteoporosis through promotion the VEGF expression and osteoblast differentiation.

摘要

微小RNA(miRNA)是一类小型非蛋白质编码RNA,作为负性基因表达调节因子发挥作用。miRNA - 210(miR - 210)最近在与血管生成相关的骨坏死发病机制中被发现。在此,我们旨在探讨miR - 210治疗绝经后骨质疏松症的临床意义。在体外检测骨髓间充质干细胞(BMSC)中miR - 210的表达,miR - 210以时间依赖性方式显著促进BMSC中血管内皮生长因子(VEGF)的表达(p<0.05)。并且miR - 210抑制PPARγ表达,但增加ALP和osterix的表达,表明miR - 210在体外抑制BMSC的脂肪细胞分化并促进其成骨细胞分化。在17β - 雌二醇(E2)处理的成骨细胞中,缺氧诱导因子1α(HIF - 1α)和VEGF的蛋白表达以剂量和时间依赖性方式显著增加(p<0.05)。并且E2通过PI3K/AKT信号通路诱导成骨细胞中VEGF的表达。综上所述,这些数据表明miR - 210通过促进VEGF表达和成骨细胞分化在改善雌激素缺乏引起的绝经后骨质疏松症中起重要作用。

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