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Publication : A functional motif of long noncoding RNA Nron against osteoporosis.

First Author  Jin F Year  2021
Journal  Nat Commun Volume  12
Issue  1 Pages  3319
PubMed ID  34083547 Mgi Jnum  J:340202
Mgi Id  MGI:6725353 Doi  10.1038/s41467-021-23642-7
Citation  Jin F, et al. (2021) A functional motif of long noncoding RNA Nron against osteoporosis. Nat Commun 12(1):3319
abstractText  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 ERalpha 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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