Liu Ke, Jing Ying, Zhang Wen, Fu Xuejie, Zhao Huan, Zhou Xichao, Tao Yunxia, Yang Huilin, Zhang Yan, Zen Ke, Zhang Chenyu, Li Donghai, Shi Qin
Orthopedic Department, the First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, No.188 Shizi Street, Suzhou 215006, PR China.
Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, No.163 Xianlin Avenue, Nanjing 210093, PR China.
Bone. 2017 Apr;97:130-138. doi: 10.1016/j.bone.2017.01.014. Epub 2017 Jan 17.
Osteoporosis is a serious health problem worldwide. MicroRNA is a post-transcriptional regulator of gene expression by either promoting mRNA degradation or interfering with mRNA translation of specific target genes. It plays a significant role in the pathogenesis of osteoporosis. Here, we first demonstrated that miR-106b (miR-106b-5p) negatively regulated osteogenic differentiation of mesenchymal stem cells in vitro. Then, we found that miR-106b expression increased in C57BL/6 mice with glucocorticoid-induced osteoporosis (GIOP), and that silencing of miR-106b signaling protected mice against GIOP through promoting bone formation and inhibiting bone resorption. At last, we showed that miR-106b inhibited osteoblastic differentiation and bone formation partly through directly targeting bone morphogenetic protein 2 (BMP2) both in vitro and in the GIOP model. Together, our findings have identified the role and mechanism of miR-106b in negatively regulating osteogenesis. Inhibition of miR-106b might be a potential new strategy for treating osteoporosis and bone defects.
骨质疏松症是全球范围内一个严重的健康问题。微小RNA是一种基因表达的转录后调节因子，可通过促进信使核糖核酸（mRNA）降解或干扰特定靶基因的mRNA翻译来发挥作用。它在骨质疏松症的发病机制中起着重要作用。在此，我们首先证明了miR-106b（miR-106b-5p）在体外对间充质干细胞的成骨分化具有负调节作用。然后，我们发现糖皮质激素诱导的骨质疏松症（GIOP）的C57BL/6小鼠中miR-106b表达增加，并且沉默miR-106b信号通路可通过促进骨形成和抑制骨吸收来保护小鼠免受GIOP影响。最后，我们表明miR-106b在体外和GIOP模型中均部分通过直接靶向骨形态发生蛋白2（BMP2）来抑制成骨细胞分化和骨形成。总之，我们的研究结果确定了miR-106b在负向调节成骨过程中的作用和机制。抑制miR-106b可能是治疗骨质疏松症和骨缺损的一种潜在新策略。
