Shijie Chen 1 2, Yuezhan Li 1, Shuang Zhi 3, Zhiyu Ding 1, Yan Huang 4, Weiguo Wang 1, Ruping Zheng 5, Haiyang Yu 5, Jianlong Wang 1, Minghua Hu 6, Jinglei Miao 1, Jinsong Li 1
Aging Dis. 2020 Oct 1;11(5):1058-1068. doi: 10.14336/AD.2019.0724. eCollection 2020 Oct.
Abstract
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.