Nat Commun:lncRNA Nron:抗骨质疏松的新型骨吸收抑制因子

2021-06-04 xiaozeng MedSci原创

骨质疏松性骨折会对老年人的健康造成灾难性的影响。

骨质疏松性骨折会对老年人的健康造成灾难性的影响。尽管目前的抑制骨吸收和合成代谢的相关骨质疏松药物可有效的抑制骨质疏松性骨折,但这两种方法均存在各种副作用。因此,鉴定用于治疗和逆转骨质疏松症的新型药物靶标迫在眉睫。

lncRNA(长链非编码RNA)已被证实是基因表达或蛋白质功能的重要调节因子。越来越多的证据表明lncRNA参与各种疾病过程,并被认为具有重要的诊断和治疗潜力。然而。其在骨吸收中的调节作用并不清楚。

为鉴定功能性lncRNA,确定lncRNA的进化保守特征是一种有效的策略 。迄今为止,尽管已鉴定出数十种进化保守的lncRNA,但仅有少数lncRNA含有保守的功能基序。此外,lncRNAs药物的副作用也不容忽视。因此,鉴定赋予lncRNAs细胞活性的功能基序有利于开发基于核酸的治疗策略。

Nron为破骨细胞的候选调控lncRNA

在该研究中,研究人员鉴定lncRNA Nron为骨吸收的关键抑制因子。研究人员发现,破骨细胞Nron敲除小鼠表现出骨吸收活性的升高以及骨质减少表型。相反的,破骨细胞Nron转基因小鼠则表现出较低的骨吸收活性和较高的骨量。

特异性敲除Nron可激活骨吸收作用

此外,药理学过表达Nron可抑制骨吸收,同时在小鼠中引发明显的副作用。为了尽量减少副作用,研究人员进一步的确定了Nron的功能基序。将Nron功能基序传递给破骨细胞能够有效地逆转骨质的流失,且没有明显的副作用。机制研究显示,Nron的功能基序能够与E3泛素连接酶CUL4B相互作用并调节ERα的稳定性。


总而言之,该研究结果揭示,lncRNA Nron是一种关键的骨吸收抑制因子,且其功能基序可潜在地用于治疗副作用风险较小的相关疾病。


原始出处:

Jin, F., Li, J., Zhang, YB. et al. A functional motif of long noncoding RNA Nron against osteoporosis. Nat Commun 12, 3319 (03 June 2021).

 

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    2022-02-09 liye789132251
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    2021-11-14 liuli5079
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    2021-06-06 xzw113
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    2021-06-06 徐岩
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    2021-06-06 Eleven17

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