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微小RNA-217通过与Runx2结合抑制大鼠骨髓间充质干细胞的成骨分化。

miR‑217 inhibits osteogenic differentiation of rat bone marrow‑derived mesenchymal stem cells by binding to Runx2.

作者信息

Zhu Yu-Long, Wang Shui, Ding De-Gang, Xu Liang, Zhu Hai-Tao

机构信息

Department of Orthopedics, Sheyang County People's Hospital, Yancheng, Jiangsu 224300, P.R. China.

出版信息

Mol Med Rep. 2017 May;15(5):3271-3277. doi: 10.3892/mmr.2017.6349. Epub 2017 Mar 22.

DOI:10.3892/mmr.2017.6349
PMID:28339007
Abstract

The elucidation of the underlying molecular mechanisms regulating the osteogenic differentiation of bone marrow‑derived mesenchymal stem cells (BMSCs) is of great importance in improving the treatment of bone‑associated diseases. MicroRNAs (miRNAs) have been proven to regulate the osteogenic differentiation of BMSCs. The present study investigated the role of miR‑217 in the osteogenic differentiation of rat BMSCs. It was observed that miR‑217 expression levels were downregulated during the process of osteogenic differentiation. Subsequently, a dual‑luciferase reporter gene assay demonstrated that miR‑217 targets a putative binding site in the 3'‑untranslated region of the runt related transcription factor 2 (Runx2) gene, which is a key transcription factor for osteogenesis. It was then demonstrated that overexpression of miR‑217 attenuated the osteogenesis of BMSCs and downregulated the expression of Runx2, whereas inhibition of miR‑217 promoted osteoblastic differentiation and upregulated Runx2 expression. Furthermore, the extracellular signal‑regulated kinase (ERK) and p38 mitogen‑activated protein kinase (p38 MAPK) signaling pathways were investigated during osteogenic induction, and the data indicated that miR‑217 may exert a negative effect on the osteogenic differentiation of BMSCs through alteration of ERK and p38 MAPK phosphorylation. The present study therefore concluded that miR‑217 functions as a negative regulator of BMSC osteogenic differentiation via the inhibition of Runx2 expression, and the underlying molecular mechanisms may partially be attributed to mediation by the ERK and p38 MAPK signaling pathways.

摘要

阐明调节骨髓间充质干细胞(BMSCs)成骨分化的潜在分子机制对于改善骨相关疾病的治疗具有重要意义。微小RNA(miRNAs)已被证明可调节BMSCs的成骨分化。本研究调查了miR-217在大鼠BMSCs成骨分化中的作用。观察到在成骨分化过程中miR-217表达水平下调。随后,双荧光素酶报告基因检测表明,miR-217靶向矮小相关转录因子2(Runx2)基因3'非翻译区的一个假定结合位点,Runx2是成骨的关键转录因子。然后证明,miR-217的过表达减弱了BMSCs的成骨作用并下调了Runx2的表达,而抑制miR-217则促进成骨细胞分化并上调Runx2表达。此外,在成骨诱导过程中研究了细胞外信号调节激酶(ERK)和p38丝裂原活化蛋白激酶(p38 MAPK)信号通路,数据表明miR-217可能通过改变ERK和p38 MAPK磷酸化对BMSCs的成骨分化产生负面影响。因此,本研究得出结论,miR-217通过抑制Runx2表达作为BMSC成骨分化的负调节因子,其潜在分子机制可能部分归因于ERK和p38 MAPK信号通路的介导。

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