Chen Chu, Tang Zuchuan, Song Qiling, Yang Min, Shi Qiong, Weng Yaguang
Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 40016, P.R. China.
Mol Med Rep. 2016 Mar;13(3):2492-8. doi: 10.3892/mmr.2016.4814. Epub 2016 Jan 27.
MicroRNAs are identified as negative regulators in gene expression through silencing gene expression at the post-transcriptional and translational levels. Bone morphogenetic protein 9 (BMP9) is the most effective in inducing osteogenesis in the BMP family, the members of which were originally identified as osteoinductive cytokines. In the current study, the role of miR‑23b in the progression of BMP9‑induced C2C12 myoblasts was investigated. The results indicated that miR‑23b was significantly downregulated in C2C12 myoblasts induced by BMP9. Overexpression of miR‑23b significantly inhibited osteogenesis in the C2C12 myoblasts. In addition, it was observed that Runx2 was negatively regulated by miR‑23b at the post‑transcriptional level, via a specific target site within the 3'UTR of Runx2. Knockdown of Runx2 promoted miR‑23b‑induced inhibition of osteogenesis in C2C12 myoblasts. The expression of Runx2 was observed to be frequently upregulated in osteoblast cell lines and inversely correlated with miR‑23b expression. Thus, the results of the present study suggest that miR‑23b inhibits BMP9‑induced C2C12 myoblast osteogenesis via targeting of the Runx2 gene, acting as a suppressor. The current study contributes to the understanding of the functions of BMP9 in ossification.
微小RNA通过在转录后和翻译水平上沉默基因表达而被鉴定为基因表达的负调节因子。骨形态发生蛋白9（BMP9）是骨形态发生蛋白家族中诱导成骨最有效的因子，该家族成员最初被鉴定为骨诱导细胞因子。在本研究中，研究了miR-23b在BMP9诱导的C2C12成肌细胞进展中的作用。结果表明，在BMP9诱导的C2C12成肌细胞中，miR-23b显著下调。miR-23b的过表达显著抑制了C2C12成肌细胞的成骨作用。此外，观察到Runx2在转录后水平上通过Runx2 3'UTR内的特定靶位点受到miR-23b的负调控。敲低Runx2促进了miR-23b诱导的C2C12成肌细胞成骨抑制。在成骨细胞系中观察到Runx2的表达经常上调，并且与miR-23b的表达呈负相关。因此，本研究结果表明，miR-23b通过靶向Runx2基因抑制BMP9诱导的C2C12成肌细胞成骨，起到抑制作用。本研究有助于理解BMP9在骨化中的功能。
