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The long noncoding RNA lnc-ob1 facilitates bone formation by upregulating Osterix in osteoblasts

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机构： [1]Department of Oral Implantology, School of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China. [2]Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, and School of Biological Science and Medical Engineering, Beihang University, Beijing, China. [3]Department of Cell Biology, and Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China. [4]Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou, China. [5]Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China. [6]The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China. [7]Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, China. [8]Department of Neurosurgery & China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.

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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. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.

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大类 | 1 区

医学

小类 | 1 区内分泌学与代谢

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第一作者机构： [1]Department of Oral Implantology, School of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.

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通讯作者：

通讯机构： [1]Department of Oral Implantology, School of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China. [2]Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, and School of Biological Science and Medical Engineering, Beihang University, Beijing, China. [3]Department of Cell Biology, and Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China. [4]Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou, China. [6]The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.

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