Bone-targeted lncRNA OGRU alleviates unloading-induced bone loss via miR-320-3p/Hoxa10 axis

• Published in: Cell death & disease Vol. 11; no. 5; p. 382
• Main Authors: Wang, Ke, Wang, Yixuan, Hu, Zebing, Zhang, Lijun, Li, Gaozhi, Dang, Lei, Tan, Yingjun, Cao, Xinsheng, Shi, Fei, Zhang, Shu, Zhang, Ge
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.05.2020; Springer Nature B.V
• Subjects: 13/51; 13/89; 14/1; 14/32; 14/63; 38/1; 38/109; 38/89; 38/90; 45/90; 631/337/384/2568; 631/80/304; 64/60; 82/1; 82/51; Animals; Antibodies; Biochemistry; Biomedical and Life Sciences; Bone Diseases, Metabolic - genetics; Bone Diseases, Metabolic - metabolism; Bone growth; Bone loss; Cell Biology; Cell Culture; Cell differentiation; Cell Differentiation - genetics; Cell Differentiation - physiology; Fractures; Hindlimb Suspension - methods; Homeobox A10 Proteins - genetics; Homeobox A10 Proteins - metabolism; Immunology; Life Sciences; Mechanical loading; Mice; MicroRNAs - genetics; Mineralization; Osteoblastogenesis; Osteoblasts - metabolism; Osteogenesis; Osteogenesis - genetics; Osteogenesis - physiology; Osteoporosis; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; Supplements; Transcription; Unloading
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-020-2574-1

Unloading-induced bone loss is a threat to human health and can eventually result in osteoporotic fractures. Although the underlying molecular mechanism of unloading-induced bone loss has been broadly elucidated, the pathophysiological role of long noncoding RNAs (lncRNAs) in this process is unknown. Here, we identified a novel lncRNA, OGRU, a 1816-nucleotide transcript with significantly decreased levels in bone specimens from hindlimb-unloaded mice and in MC3T3-E1 cells under clinorotation-unloading conditions. OGRU overexpression promoted osteoblast activity and matrix mineralization under normal loading conditions, and attenuated the suppression of MC3T3-E1 cell differentiation induced by clinorotation unloading. Furthermore, this study found that supplementation of pcDNA3.1(+)–OGRU via (DSS) 6 –liposome delivery to the bone-formation surfaces of hindlimb-unloaded (HLU) mice partially alleviated unloading-induced bone loss. Mechanistic investigations demonstrated that OGRU functions as a competing endogenous RNA (ceRNA) to facilitate the protein expression of Hoxa10 by competitively binding miR-320-3p and subsequently promote osteoblast differentiation and bone formation. Taken together, the results of our study provide the first clarification of the role of lncRNA OGRU in unloading-induced bone loss through the miR-320-3p/Hoxa10 axis, suggesting an efficient anabolic strategy for osteoporosis treatment.