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.

The exercise-induced long noncoding RNA CYTOR promotes fast-twitch myogenesis in aging

“…lncRNAs can also easily be synthesized and delivered using chemically modified lipid nanoparticles or exosomes to improve RNA stability and increase tissue specificity. Recent advances have identified short, functionally active fragments of lncRNAs (“lncRNA mimics”), which mimic the effect of the full-length lncRNA ( 91 , 92 ). These fragments might have reduced immunogenicity and can potentially be modified to increase in vivo stability and tagged with organ-targeting peptides to improve tissue specificity.…”

Promising Advances in LINC01116 Related to Cancer

“…Owing to the development of multiple RNA detection techniques ( Shu et al, 2021 ; Toden et al, 2021 ; Wang et al, 2021 ; Zhong et al, 2021a ), most RNAs have been found to lack the capacity to encode proteins. Although these RNAs do not directly translate into proteins ( Gupta et al, 2020 ), driving evidence clarifies that they play an essential role in biological functions ( Chen et al, 2020b ; Jantrapirom et al, 2021 ; Jin et al, 2021 ; Lai et al, 2021 ; Zhang et al, 2021b ). Such is the case of long non-coding RNAs (lncRNAs), which are no less than 200 nucleotides and participate in the initiation and progression of various diseases, especially cancers ( Chen et al, 2020a ; Huang et al, 2021 ; Kotani et al, 2021 ; Luo et al, 2021 ; Teng et al, 2021 ).…”

DANCR Mediates the Rescuing Effects of Sesamin on Postmenopausal Osteoporosis Treatment via Orchestrating Osteogenesis and Osteoclastogenesis

“…However, the biological role of lncRNA in regulating osteoclast differentiation in vitro and controlling bone resorption in vivo is less studied yet. Wang's group identified the functional motif a lncRNA Nron that could regulate ERα stability to prevent bone loss [29]. In the present study, we have identified the lncRNA DANCR a key factor for sesamin-mediated osteogenesis and osteoclastogenesis, as well as the regulator in osteoporosis pathogenesis.…”