lncRNA Xist Regulates Osteoblast Differentiation by Sponging miR-19a-3p in Aging-induced Osteoporosis.
lncRNA Xist Regulates Osteoblast Differentiation by Sponging miR-19a-3p in Aging-induced Osteoporosis.
复制标题
lncRNA Xist 通过海绵 miR-19a-3p 在衰老引起的骨质疏松症中调节成骨细胞分化。
DOI：
10.14336/ad.2019.0724
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发表时间：
2020-10
影响因子：
7.4
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Chen S;Li Y;Zhi S;Ding Z;Huang Y;Wang W;Zheng R;Yu H;Wang J;Hu M;Miao J;Li J
骨髓间充质干细胞（BMSCs）在成骨分化和脂肪分化之间的转换在衰老性骨质疏松症中起关键作用。在本研究中，miR-19a-3p在老年人和小鼠骨髓间充质干细胞中明显下调。过表达的miR-19a-3p明显减少小鼠衰老诱导的骨质流失，促进骨髓间充质干细胞成骨分化，而沉默的miR-19a-3p明显增加小鼠衰老诱导的骨质流失，抑制骨髓间充质干细胞成骨分化。Hoxa5在老年小鼠骨髓间充质干细胞中显著下调，并作为miR-19a-3p的直接靶基因参与miR-19a-3p诱导的成骨细胞分化。此外，lncRNA Xist被发现作为miR-19a-3p的海绵抑制骨髓间充质干细胞成骨分化。总之，我们的研究揭示了lncRNA Xist/miR-19a-3p/Hoxa5通路在衰老诱导的BMSCs成骨分化中的关键作用，提示了骨质疏松症的潜在治疗靶点。
The switch between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) plays a key role in aging-induced osteoporosis. In this study, miR-19a-3p was obviously downregulated in BMSCs from aged humans and mice. Overexpressed miR-19a-3p evidently reduced aging-induced bone loss in mice and promoted osteogenic differentiation of BMSCs, while silenced miR-19a-3p manifestly increased aging-induced bone loss in mice and repressed osteogenic differentiation of BMSCs. Hoxa5 was significantly downregulated in the BMSCs from aged mice and contribute to miR-19a-3p-induced osteoblast differentiation as a direct target gene of miR-19a-3p. Furthermore, lncRNA Xist was found as a sponge of miR-19a-3p to repress BMSCs osteogenic differentiation. In conclusion, our study reveals the critical role of the lncRNA Xist/miR-19a-3p/Hoxa5 pathway in aging-induced osteogenic differentiation of BMSCs, indicating the potential therapeutic target for osteoporosis.