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A functional motif of long noncoding RNA Nron against osteoporosis.

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.

SUBMITTER: Jin F

PROVIDER: S-EPMC8175706 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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A functional motif of long noncoding RNA Nron against osteoporosis.

Jin Fujun F Li Junhui J Zhang Yong-Biao YB Liu Xiangning X Cai Mingxiang M Liu Meijing M Li Mengyao M Ma Cui C Yue Rui R Zhu Yexuan Y Lai Renfa R Wang Zuolin Z Ji Xunming X Wei Huawei H Dong Jun J Liu Zhiduo Z Wang Yifei Y Sun Yao Y Wang Xiaogang X

Nature communications 20210603 1

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 inhib ...[more]

PMID: 34083547

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A functional motif of long noncoding RNA Nron against osteoporosis.

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A functional motif of long noncoding RNA Nron against osteoporosis.

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