Li Hongqiu, Yang Feng, Wang Zhe, Fu Qin, Liang A
Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang 110004, P.R. China.
Department of Radiology, Central Hospital of Shenyang Medical College, Shenyang 110024, P.R. China.
Mol Med Rep. 2015 Jul;12(1):1561-7. doi: 10.3892/mmr.2015.3497. Epub 2015 Mar 17.
Previous studies have suggested that microRNAs (miRNAs/miRs) may positively or negatively control osteogenic differentiation and mineralization by targeting negative regulators of osteogenesis or important osteogenic factors. miR-21 is important in osteoblast differentiation and Smad7 is a critical regulator of osteogenic differentiation, which inhibits proliferation, differentiation and mineralization in mouse osteoblast cells. However, the association between Smad7 and miR-21 remain to be elucidated. In the present study, miR-21 was found to promote the level of osteogenic differentiation and increase matrix mineralization in MC3T3-E1 cells. Furthermore, Smad7 was identified as a direct target of miR-21 in the MC3T3-E1 cells. The overexpression of miR-21 affected the protein levels of SMAD7, but not the mRNA levels, which suggested that miR-21 regulates the levels of SMAD7 by inhibiting translation, rather than by promoting mRNA decay. Forced expression of miR-21 promoted osteogenic differentiation and mineralization, while inhibition of miR-21 suppressed these processes. The present study also identified for the first time, to the best of our knowledge, the promotion of osteogenic differentiation and mineralization by miR-21, by repressing the expression of Smad7.
先前的研究表明，微小RNA（miRNA/miR）可能通过靶向成骨作用的负调节因子或重要的成骨因子，对成骨分化和矿化产生正向或负向调控作用。miR-21在成骨细胞分化中起重要作用，而Smad7是成骨分化的关键调节因子，它抑制小鼠成骨细胞的增殖、分化和矿化。然而，Smad7与miR-21之间的关联仍有待阐明。在本研究中，发现miR-21可促进MC3T3-E1细胞的成骨分化水平并增加基质矿化。此外，Smad7被确定为MC3T3-E1细胞中miR-21的直接靶点。miR-21的过表达影响SMAD7的蛋白水平，但不影响mRNA水平，这表明miR-21通过抑制翻译而非促进mRNA降解来调节SMAD7的水平。miR-21的强制表达促进成骨分化和矿化，而抑制miR-21则抑制这些过程。据我们所知，本研究还首次发现miR-21通过抑制Smad7的表达促进成骨分化和矿化。
