Long noncoding RNAs (lncRNAs) have emerged as integral regulators of physiology and disease, but specific roles of lncRNAs in bone disease remain largely unknown. Here, we show that lnc-ob1 regulates osteoblast activity and bone formation in mice by upregulating the osteogenic transcription factor Osterix. Expression of lnc-ob1 is enriched in osteoblasts and upregulated during osteoblastogenesis. We demonstrate that osteoblast-specific knock-in of lnc-ob1 enhances bone formation and increases bone mass. Pharmacological overexpression of lnc-ob1 specifically in osteoblasts confers resistance to ovariectomy-induced osteoporosis in mice. In humans, expression of the homologue, lnc-OB1, decreases with age in osteoblasts of patients with osteoporosis. Mechanistically, lnc-ob1 upregulates the expression of Osterix in mouse and human osteoblasts, probably via inhibition of H3K27me3 methylation. Our data indicate that lnc-OB1 regulates bone formation and might be a drug target for the treatment of osteoporosis.
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The high-throughput RNA-seq data have been deposited in NCBI under accession code GSE112318. The data that support the findings of this study are available from the authors on reasonable request, see author contributions for specific datasets.
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This research was supported by grants from the National key research and development program (2016YFC102705/2017YFA0505001/2018YFC0910200); National Natural Science Foundation Projects (No. 81822012, 81771043, 81770873, 81722031, 81470715, 81771043, 31671312, 3137134); 2017BR009, 2014BAI04B07 and Kx0200020173386, Guangdong Natural Science Funds (no. 2014A030313358), the Major Project in Guangdong Province of Science (no. 2014KZDXM011) and Guangdong Natural Science Funds for Distinguished Young Scholars (no. S2013050013880). We thank C. Qin for providing the DMP1 antibody as a gift. We thank Y. Zhang and S. Gao at Tongji University for providing critical comments and technical support. We thank J. Li for help with the style of the manuscript.
The authors declare no competing interests.
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Sun, Y., Cai, M., Zhong, J. et al. The long noncoding RNA lnc-ob1 facilitates bone formation by upregulating Osterix in osteoblasts. Nat Metab 1, 485–496 (2019). https://doi.org/10.1038/s42255-019-0053-8
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