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雌激素通过 miR-532-3p/SIRT1 轴促进 lncRNA H19 的表达来调节 BMSCs 的成骨分化,减少骨质疏松症。

Estrogen promotes lncRNA H19 expression to regulate osteogenic differentiation of BMSCs and reduce osteoporosis via miR-532-3p/SIRT1 axis.

机构信息

Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei Province, PR China.

Department of Urology Surgery, Henan Provincial People's Hospital; People's Hospital of Zhengzhou University, Zhengzhou, 450003, Henan Province, PR China.

出版信息

Mol Cell Endocrinol. 2021 May 1;527:111171. doi: 10.1016/j.mce.2021.111171. Epub 2021 Feb 9.

Abstract

Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) plays an essential role in bone formation. Its imbalance can lead to osteoporosis. Estrogen and long noncoding RNAs (lncRNAs) have been confirmed to participate in osteogenesis. However, the underlying mechanism remains unclear. The purpose of our study was to explore the function of lncRNA H19 in estrogen-induced osteogenic differentiation of BMSCs. The present research demonstrated that the expression levels of lncRNA H19 and SIRT1 were markedly downregulated in postmenopausal osteoporosis (PMOP), while miR-532-3p expression was obviously increased. Moreover, estrogen induced the osteogenic differentiation of BMSCs by upregulating lncRNA H19. Furthermore, our integrated experiments showed that lncRNA H19 caused a decrease in the expression of miR-532-3p, which was verified to target SIRT1 directly. Additionally, estrogen alleviated osteoporosis in OVX rats through lncRNA H19-mediated miR-532-3p/SIRT1 axis. Our findings imply that lncRNA H19 mediates estrogen-regulated osteogenic differentiation in BMSCs via miR-532-3p/SIRT1 signalling and may become a novel target for alleviating PMOP.

摘要

骨髓间充质干细胞(BMSCs)的成骨分化在骨形成中起着至关重要的作用。其失衡可导致骨质疏松症。雌激素和长链非编码 RNA(lncRNA)已被证实参与成骨作用。然而,其潜在的机制仍不清楚。我们的研究旨在探讨 lncRNA H19 在雌激素诱导的 BMSCs 成骨分化中的作用。本研究表明,绝经后骨质疏松症(PMOP)中 lncRNA H19 和 SIRT1 的表达水平明显下调,而 miR-532-3p 的表达明显增加。此外,雌激素通过上调 lncRNA H19 诱导 BMSCs 的成骨分化。此外,我们的综合实验表明,lncRNA H19 导致 miR-532-3p 的表达减少,并且被证明确实直接靶向 SIRT1。此外,雌激素通过 lncRNA H19 介导的 miR-532-3p/SIRT1 轴减轻 OVX 大鼠的骨质疏松症。我们的研究结果表明,lncRNA H19 通过 miR-532-3p/SIRT1 信号转导介导雌激素调节的 BMSCs 成骨分化,可能成为缓解 PMOP 的新靶点。

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