Zhao Weigong, Wu Caijun, Dong Yanying, Ma Yunfeng, Jin Yaofeng, Ji Yanhong
Department of Orthopedics, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China.
Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
Int J Mol Sci. 2015 May 21;16(5):11699-712. doi: 10.3390/ijms160511699.
MicroRNAs (miRNAs) have been reported to have diverse biological roles in regulating many biological processes, including osteogenic differentiation. In the present study, we identified that miR-24 was a critical regulator during osteogenic differentiation. We found that overexpression of miR-24 significantly inhibited osteogenic differentiation, which decreased alkaline phosphatase activity, matrix mineralization and the expression of osteogenic differentiation markers. In contrast, inhibition of miR-24 exhibited an opposite effect. Furthermore, we delineated that miR-24 regulates post-transcriptionals of T-cell factor-1 (Tcf-1) via targeting the 3'-untranslated region (UTR) of Tcf-1 mRNA. MiR-24 was further found to regulate the protein expression of Tcf-1 in the murine osteoprogenitors cells and bone mesenchymal stem cells. Additionally, the positive effect of miR-24 suppression on osteoblast differentiation was apparently abrogated by Tcf-1 silencing. Taken together, our data suggest that miR-24 participates in osteogenic differentiation by targeting and regulating Tcf-1 expression in osteoblastic cells.
据报道,微小RNA(miRNA)在调节包括成骨分化在内的许多生物学过程中具有多种生物学作用。在本研究中,我们确定miR-24是成骨分化过程中的关键调节因子。我们发现,miR-24的过表达显著抑制成骨分化,降低碱性磷酸酶活性、基质矿化以及成骨分化标志物的表达。相反,抑制miR-24则表现出相反的效果。此外,我们还阐明miR-24通过靶向T细胞因子1(Tcf-1)mRNA的3'非翻译区(UTR)来调节Tcf-1的转录后水平。进一步发现,miR-24可调节小鼠成骨祖细胞和骨髓间充质干细胞中Tcf-1的蛋白表达。此外,Tcf-1沉默明显消除了miR-24抑制对成骨细胞分化的积极作用。综上所述,我们的数据表明,miR-24通过靶向和调节成骨细胞中Tcf-1的表达来参与成骨分化。