A functional motif of long noncoding RNA Nron against osteoporosis

Fujun Jin, Junhui Li, Yong-Biao Zhang, Xiangning Liu, Mingxiang Cai, Meijing Liu, Mengyao Li, Cui Ma, Rui Yue, Yexuan Zhu, Renfa Lai, Zuolin Wang, Xunming Ji, Huawei Wei, Jun Dong, Zhiduo Liu, Yifei Wang (), Yao Sun () and Xiaogang Wang ()
Additional contact information
Fujun Jin: The First Affiliated Hospital of Jinan University & Department of Stomatology, College of stomatology, Jinan University
Junhui Li: Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration
Yong-Biao Zhang: Beihang University
Xiangning Liu: The First Affiliated Hospital of Jinan University & Department of Stomatology, College of stomatology, Jinan University
Mingxiang Cai: The First Affiliated Hospital of Jinan University & Department of Stomatology, College of stomatology, Jinan University
Meijing Liu: Beihang University
Mengyao Li: Shanghai Jiao Tong University School of Medicine
Cui Ma: Beihang University
Rui Yue: Tongji University
Yexuan Zhu: Jinan University
Renfa Lai: The First Affiliated Hospital of Jinan University & Department of Stomatology, College of stomatology, Jinan University
Zuolin Wang: Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration
Xunming Ji: Xuanwu Hospital, Capital Medical University
Huawei Wei: Zeki Biotechnology & Pharmaceutical Co. Ltd
Jun Dong: Jinan University
Zhiduo Liu: Shanghai Jiao Tong University School of Medicine
Yifei Wang: Jinan University
Yao Sun: Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration
Xiaogang Wang: The First Affiliated Hospital of Jinan University & Department of Stomatology, College of stomatology, Jinan University

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract Long noncoding RNAs are widely implicated in diverse disease processes. Nonetheless, their regulatory roles in bone resorption are undefined. Here, we identify lncRNA Nron as a critical suppressor of bone resorption. We demonstrate that osteoclastic Nron knockout mice exhibit an osteopenia phenotype with elevated bone resorption activity. Conversely, osteoclastic Nron transgenic mice exhibit lower bone resorption and higher bone mass. Furthermore, the pharmacological overexpression of Nron inhibits bone resorption, while caused apparent side effects in mice. To minimize the side effects, we further identify a functional motif of Nron. The delivery of Nron functional motif to osteoclasts effectively reverses bone loss without obvious side effects. Mechanistically, the functional motif of Nron interacts with E3 ubiquitin ligase CUL4B to regulate ERα stability. These results indicate that Nron is a key bone resorption suppressor, and the lncRNA functional motif could potentially be utilized to treat diseases with less risk of side effects.

Date: 2021
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DOI: 10.1038/s41467-021-23642-7

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