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miR-877-3p promotes TGF-β1-induced osteoblast differentiation of MC3T3-E1 cells by targeting Smad7

机译:miR-877-3p通过靶向Smad7促进TGF-β1诱导的MC3T3-E1细胞成骨细胞分化

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摘要

MicroRNAs (miRNAs) are emerging as important regulators of various physiological and pathological processes and may serve key roles in the maintenance of bone homeostasis via effects on osteoblast differentiation. The aim of the present study was to define the role of miR-877-3p in osteoblast differentiation using MC3T3-E1 cells, an osteoblast precursor cell line. It was demonstrated using RT-qPCR analysis that miR-877-3p was gradually increased in MC3T3-E1 cells during the osteoblastic differentiation induced by transforming growth factor (TGF)-β1. Gain-of-function and loss-of-function experiments revealed that the overexpression of miR-877-3p promoted the osteoblastic differentiation of MC3T3-E1 cells, whereas depletion of miR-877-3p inhibited this process in vitro and in vivo. Bioinformatics analysis and validation experiments demonstrated that Smad7, which acts as a negative regulator of osteogenesis, was a target of miR-877-3p. Furthermore, the overexpression of Smad7 partially reversed the osteoblastic differentiation of MC3T3-E1 cells induced by miR-877-3p. In conclusion, the results of the present study suggest that the miR-877-3p/Smad7 axis is associated with the osteoblastic differentiation of MC3T3-E1 cells and may indicate a potential therapeutic approach for osteogenesis disorders.
机译:MicroRNA(miRNA)逐渐成为各种生理和病理过程的重要调节剂,并可能通过对成骨细胞分化的影响而在维持骨稳态中发挥关键作用。本研究的目的是使用成骨细胞前体细胞系MC3T3-E1细胞来定义miR-877-3p在成骨细胞分化中的作用。使用RT-qPCR分析证明,在转化生长因子(TGF)-β1诱导的成骨细胞分化过程中,miR-877-3p在MC3T3-E1细胞中逐渐增加。功能获得和功能丧失实验表明,miR-877-3p的过表达促进了MC3T3-E1细胞的成骨细胞分化,而miR-877-3p的消耗在体外和体内均抑制了该过程。生物信息学分析和验证实验表明,Smad7是miR-877-3p的靶标,Smad7是成骨作用的负调节剂。此外,Smad7的过度表达部分逆转了miR-877-3p诱导的MC3T3-E1细胞的成骨细胞分化。总之,本研究的结果表明,miR-877-3p / Smad7轴与MC3T3-E1细胞的成骨细胞分化有关,并可能指示成骨疾病的潜在治疗方法。

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