Department of Neurosurgery, Beijing Chao-Yang Hospital, Beijing, P.R. China.
Eur Rev Med Pharmacol Sci. 2018 Jun;22(11):3318-3326. doi: 10.26355/eurrev_201806_15151.
To investigate the role of miR-29a in regulating the differentiation mesenchymal stem cells into osteoblasts.
For the first step, the changes of expression of miR-29a during the process of mesenchymal stem cells (MSCs) differentiation into osteoblast were detected. Then, we infected the MSCs with mimics or inhibitors of miR-29a to explore the roles of miR-29a in the differentiation. Further, the prediction and verification of the possible target genes of miR-29a were achieved by bioinformatics analysis and luciferase reporter assay.
MiR-29a was up-regulated during the process of MSCs differentiation into osteoblasts. Overexpression or inhibition of miR-29a using mimics or inhibitors had no significant effect on cell proliferation. Furthermore, the differentiation was enhanced when miR-29a was artificially overexpressed in vitro, whereas silencing of miR-29a attenuated this process. It was evidenced by alkaline phosphatase (ALP) staining, matrix mineralization, and increased expression of osteoblast-specific genes. Furthermore, we determined that the gene HDAC4 might be a direct target of miR-29a.
In the current study, miR-29a promotes osteogenesis via suppressing HDAC4, indicating that targeting miR-29a may be feasible in the management of osteoporosis.
研究 miR-29a 在调控间充质干细胞向成骨细胞分化中的作用。
首先，检测 miR-29a 在间充质干细胞（MSCs）向成骨细胞分化过程中的表达变化。然后，我们用 miR-29a 的模拟物或抑制剂感染 MSCs，以探讨 miR-29a 在分化中的作用。进一步通过生物信息学分析和荧光素酶报告基因实验预测和验证 miR-29a 的可能靶基因。
miR-29a 在 MSCs 向成骨细胞分化过程中上调。使用模拟物或抑制剂过表达或抑制 miR-29a 对细胞增殖没有显著影响。此外，体外人工过表达 miR-29a 增强了分化，而沉默 miR-29a 则减弱了这一过程。碱性磷酸酶（ALP）染色、基质矿化和骨细胞特异性基因表达增加证实了这一点。此外，我们确定 HDAC4 基因可能是 miR-29a 的直接靶基因。
在本研究中，miR-29a 通过抑制 HDAC4 促进成骨作用，表明靶向 miR-29a 可能在骨质疏松症的治疗中是可行的。
