长链非编码RNA Xist通过海绵化miR-19a-3p调控衰老诱导的骨质疏松症中的成骨细胞分化

lncRNA Xist Regulates Osteoblast Differentiation by Sponging miR-19a-3p in Aging-induced Osteoporosis.

作者信息

Chen Shijie, Li Yuezhan, Zhi Shuang, Ding Zhiyu, Huang Yan, Wang Weiguo, Zheng Ruping, Yu Haiyang, Wang Jianlong, Hu Minghua, Miao Jinglei, Li Jinsong

机构信息

1Department of Orthopaedics, The Third Xiangya Hospital of Central South University, Changsha, China.

2Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.

出版信息

Aging Dis. 2020 Oct 1;11(5):1058-1068. doi: 10.14336/AD.2019.0724. eCollection 2020 Oct.

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.

骨髓间充质干细胞（BMSCs）成骨与成脂分化之间的转换在衰老诱导的骨质疏松症中起关键作用。在本研究中，miR-19a-3p在老年人类和小鼠的BMSCs中明显下调。过表达miR-19a-3p明显减少了小鼠衰老诱导的骨质流失，并促进了BMSCs的成骨分化，而沉默miR-19a-3p则明显增加了小鼠衰老诱导的骨质流失，并抑制了BMSCs的成骨分化。Hoxa5在老年小鼠的BMSCs中显著下调，并作为miR-19a-3p的直接靶基因促进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BMSCs的成骨分化。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，为骨质疏松症指明了潜在的治疗靶点。