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miR-483-3p 通过靶向 STAT1 调节骨髓间充质干细胞的成骨分化。

miR‑483‑3p regulates osteogenic differentiation of bone marrow mesenchymal stem cells by targeting STAT1.

机构信息

Department of Endocrinology, Endocrinology Research Center, Central South University, Changsha, Hunan 410008, P.R. China.

Department of Medicine, Hunan University of Medicine, Huaihua, Hunan 418000, P.R. China.

出版信息

Mol Med Rep. 2019 Nov;20(5):4558-4566. doi: 10.3892/mmr.2019.10700. Epub 2019 Sep 24.

Abstract

Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is regulated by a variety of intracellular regulatory factors including osterix, runt‑related transcription factor 2 (RUNX2), bone morphogenetic proteins and transforming growth factorβ. Recent studies have shown that microRNAs (miRs) serve a crucial role in this process. In the present study, miR‑483‑3p levels were significantly increased during osteogenic differentiation of mouse and human BMSCs. Overexpression of miR‑483‑3p promoted osteogenic differentiation, whereas inhibition of miR‑483‑3p reversed these effects. miR‑483‑3p regulated osteogenic differentiation of BMSCs by targeting STAT1, and thus enhancing RUNX2 transcriptional activity and RUNX2 nuclear translocation. In vivo, overexpression of miR‑483‑3p using a BMSC‑specific aptamer delivery system stimulated bone formation in aged mice. Therefore, the present study suggested that miR‑483‑3p promoted osteogenic differentiation of BMSCs by targeting STAT1, and miR‑483‑3 prepresent a potential therapeutic target for age‑related bone loss.

摘要

成骨分化的骨髓间充质干细胞(BMSCs)受多种细胞内调节因子的调节,包括osterix、runt 相关转录因子 2(RUNX2)、骨形态发生蛋白和转化生长因子β。最近的研究表明,微小 RNA(miRs)在这个过程中起着至关重要的作用。在本研究中,miR-483-3p 在小鼠和人 BMSCs 的成骨分化过程中水平显著升高。miR-483-3p 的过表达促进成骨分化,而抑制 miR-483-3p 则逆转了这些效应。miR-483-3p 通过靶向 STAT1 调节 BMSCs 的成骨分化,从而增强 RUNX2 的转录活性和 RUNX2 的核转位。在体内,使用 BMSC 特异性适体递送系统过表达 miR-483-3p 可刺激老年小鼠的骨形成。因此,本研究表明 miR-483-3p 通过靶向 STAT1 促进 BMSCs 的成骨分化,miR-483-3p 可能成为与年龄相关的骨丢失的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a520/6797999/916dc55f5729/MMR-20-05-4558-g00.jpg

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