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

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

doi:10.14336/AD.2019.0724

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

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

Authors

Shijie Chen^{1

2}, Yuezhan Li¹, Shuang Zhi³, Zhiyu Ding¹, Yan Huang⁴, Weiguo Wang¹, Ruping Zheng⁵, Haiyang Yu⁵, Jianlong Wang¹, Minghua Hu⁶, Jinglei Miao¹, Jinsong Li¹

Affiliations

¹ 1Department of Orthopaedics, The Third Xiangya Hospital of Central South University, Changsha, China.
² 2Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
³ 4Four Gynecological Wards, Ningbo Women & Children's Hospital, Ningbo, Zhejiang, China.
⁴ 5The Second Xiangya Hospital of Central South University, Changsha, China.
⁵ 6School of Basic Medical Science, Central South University, Changsha, China.
⁶ 3Department of Anatomy, Histology and Embryology, Changsha Medical University, Changsha, China.

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.

Keywords: BMSCs; Hoxa5; Osteoporosis; lncRNA Xist; miR-19a-3p.