Silencing miR-106b accelerates osteogenesis of mesenchymal stem cells and rescues against glucocorticoid-induced osteoporosis by targeting BMP2

Silencing miR-106b accelerates osteogenesis of mesenchymal stem cells and rescues against glucocorticoid-induced osteoporosis by targeting BMP2
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沉默 miR-106b 可加速间充质干细胞的成骨,并通过靶向 BMP2 来对抗糖皮质激素诱导的骨质疏松症

DOI:
10.1016/j.bone.2017.01.014
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发表时间:
2017-04-01
期刊:
影响因子:
4.1
通讯作者:
Shi, Qin
Shi, Qin
中科院分区:
医学2区
文献类型:
--
作者:
Liu, Ke;Jing, Ying;Shi, Qin

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骨质疏松症是一个严重的全球性健康问题。MicroRNA是一种转录后基因表达调控因子,通过促进mRNA降解或干扰特定靶基因的mRNA翻译。它在骨质疏松症的发病机制中起重要作用。在此,我们首次证明了miR-106 b(miR-106 b-5 p)在体外负调控间充质干细胞的成骨分化。随后,我们发现miR-106 b在糖皮质激素诱导的骨质疏松症(GIOP)C57 BL/6小鼠中表达增加,沉默miR-106 b信号通路可通过促进骨形成和抑制骨吸收保护小鼠免受GIOP的影响。最后,我们发现miR-106 b在体外和GIOP模型中部分通过直接靶向骨形态发生蛋白2(BMP 2)抑制成骨细胞分化和骨形成。总之,我们的研究结果已经确定了miR-106 b在负调控骨生成中的作用和机制。抑制miR-106 b可能是治疗骨质疏松和骨缺损的一种潜在新策略。(C)2017由Elsevier出版
Osteoporosis is a serious health problem worldwide. MicroRNA is a post-transcriptional regulator of gene expression by either promoting mRNA degradation or interfering with mRNA translation of specific target genes. It plays a significant role in the pathogenesis of osteoporosis. Here, we first demonstrated that miR-106b (miR-106b-5p) negatively regulated osteogenic differentiation of mesenchymal stem cells in vitro. Then, we found that miR-106b expression increased in C57BL/6 mice with glucocorticoid-induced osteoporosis (GIOP), and that silencing of miR-106b signaling protected mice against GIOP through promoting bone formation and inhibiting bone resorption. At last, we showed that miR-106b inhibited osteoblastic differentiation and bone formation partly through directly targeting bone morphogenetic protein 2 (BMP2) both in vitro and in the GIOP model. Together, our findings have identified the role and mechanism of miR-106b in negatively regulating osteogenesis. Inhibition of miR-106b might be a potential new strategy for treating osteoporosis and bone defects. (C) 2017 Published by Elsevier