2. Academic Validation
  3. A functional motif of long noncoding RNA Nron against osteoporosis

A functional motif of long noncoding RNA Nron against osteoporosis

  • Nat Commun. 2021 Jun 3;12(1):3319. doi: 10.1038/s41467-021-23642-7.
Fujun Jin  # 1 2,  Junhui Li  # 3,  Yong-Biao Zhang  # 2,  Xiangning Liu  # 1 4,  Mingxiang Cai 1 3,  Meijing Liu 2,  Mengyao Li 5,  Cui Ma 2,  Rui Yue 6,  Yexuan Zhu 4,  Renfa Lai 1,  Zuolin Wang 3,  Xunming Ji 7,  Huawei Wei 8,  Jun Dong 4,  Zhiduo Liu 5,  Yifei Wang 9,  Yao Sun 10,  Xiaogang Wang 11 12
Affiliations

Affiliations

  • 1 Clinical Research Platform for Interdiscipline of Stomatology, The First Affiliated Hospital of Jinan University & Department of Stomatology, College of stomatology, Jinan University, Guangzhou, China.
  • 2 Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, China.
  • 3 Department of Oral Implantology, School of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.
  • 4 Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China.
  • 5 Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 6 Institute for Regenerative Medicine, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
  • 7 Department of Neurosurgery & China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.
  • 8 Zeki Biotechnology & Pharmaceutical Co. Ltd, Beijing, China.
  • 9 Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China. twangyf@jnu.edu.cn.
  • 10 Department of Oral Implantology, School of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China. yaosun@tongji.edu.cn.
  • 11 Clinical Research Platform for Interdiscipline of Stomatology, The First Affiliated Hospital of Jinan University & Department of Stomatology, College of stomatology, Jinan University, Guangzhou, China. xiaogangwang@buaa.edu.cn.
  • 12 Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, China. xiaogangwang@buaa.edu.cn.
  • # Contributed equally.
PMID: 34083547 DOI: 10.1038/s41467-021-23642-7
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.

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