He Guisong, Chen Jianming, Huang Dong
Department of Orthopedics, The Third School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510000, P.R. China.
Department of Orthopedics, Guangdong Provincial Second People's Hospital, Guangzhou, Guangdong 510220, P.R. China.
Exp Ther Med. 2019 Jul;18(1):312-319. doi: 10.3892/etm.2019.7570. Epub 2019 May 10.
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 and . 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.
微小RNA(miRNA)正逐渐成为各种生理和病理过程的重要调节因子,并可能通过影响成骨细胞分化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细胞来确定miR-877-3p在成骨细胞分化中的作用。通过RT-qPCR分析表明,在转化生长因子(TGF)-β1诱导的MC3T3-E1细胞成骨分化过程中,miR-877-3p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细胞的成骨分化,而miR-877-3p的缺失则抑制了这一过程。生物信息学分析和验证实验表明,作为成骨负调节因子的Smad7是miR-877-3p的靶标。此外,Smad7的过表达部分逆转了miR-877-3p诱导的MC3T3-E1细胞的成骨分化。总之,本研究结果表明,miR-877-3p/Smad7轴与MC3T3-E1细胞的成骨分化相关,并可能为成骨障碍指明一种潜在的治疗方法。