Targeted overexpression of the long noncoding RNA ODSM can regulate osteoblast function in vitro and in vivo

• Published in: Cell death & disease Vol. 11; no. 2; p. 133
• Main Authors: Wang, Yixuan, Wang, Ke, Zhang, Lijun, Tan, Yingjun, Hu, Zebing, Dang, Lei, Zhou, Hua, Li, Gaozhi, Wang, Han, Zhang, Shu, Shi, Fei, Cao, Xinsheng, Zhang, Ge
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.02.2020; Springer Nature B.V
• Subjects: 13/1; 13/109; 13/2; 13/31; 13/89; 38/61; 38/77; 3T3 Cells; 631/337; 64/60; 692/699; Animals; Antibodies; Apoptosis; Biochemistry; Biomedical and Life Sciences; Bone loss; Cell Biology; Cell Culture; Cell Differentiation; Disease Models, Animal; ets-Domain Protein Elk-1 - genetics; ets-Domain Protein Elk-1 - metabolism; Gene Targeting; Hindlimb Suspension; Immunology; Life Sciences; Male; Mechanical unloading; Mice; Mice, Inbred C57BL; Microgravity; MicroRNAs - genetics; MicroRNAs - metabolism; Mineralization; Osteoblastogenesis; Osteoblasts; Osteoblasts - metabolism; Osteoblasts - pathology; Osteogenesis; Osteopenia; Osteoporosis; Osteoporosis - genetics; Osteoporosis - metabolism; Osteoporosis - pathology; Osteoporosis - prevention & control; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal Transduction; Supplements; Up-Regulation; Weightlessness Simulation
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-020-2325-3

Ameliorating bone loss caused by mechanical unloading is a substantial clinical challenge, and the role of noncoding RNAs in this process has attracted increasing attention. In this study, we found that the long noncoding RNA osteoblast differentiation-related lncRNA under simulated microgravity (lncRNA ODSM) could inhibit osteoblast apoptosis and promote osteoblast mineralization in vitro. The increased expression level of the lncRNA ODSM partially reduced apoptosis and promoted differentiation in MC3T3-E1 cells under microgravity unloading conditions, and the effect was partially dependent on miR-139-3p. LncRNA ODSM supplementation in hindlimb-unloaded mice caused a decrease in the number of apoptotic cells in bone tissue and an increase in osteoblast activity. Furthermore, targeted overexpression of the lncRNA ODSM in osteoblasts partially reversed bone loss induced by mechanical unloading at the microstructural and biomechanical levels. These findings are the first to suggest the potential value of the lncRNA ODSM in osteoporosis therapy and the treatment of pathological osteopenia.