Bone-targeted lncRNA OGRU alleviates unloading-induced bone loss via miR-320-3p/Hoxa10 axis
Bone-targeted lncRNA OGRU alleviates unloading-induced bone loss via miR-320-3p/Hoxa10 axis
复制标题
骨靶向lncRNA OGRU通过miR-320-3p/Hoxa10轴减轻卸载引起的骨丢失
DOI：
10.1038/s41419-020-2574-1
复制
发表时间：
2020-05-19
影响因子：
9
通讯作者：
Zhang, Ge
中科院分区：
文献类型：
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作者：
Wang, Ke;Wang, Yixuan;Zhang, Ge
卸荷引起的骨丢失是对人类健康的威胁，并可最终导致骨质疏松性骨折。尽管卸载诱导的骨丢失的潜在分子机制已被广泛阐明，但长链非编码RNA（lncRNA）在此过程中的病理生理作用尚不清楚。在这里，我们确定了一种新的lncRNA，OGRU，一个1816个核苷酸的转录物，在后肢卸载小鼠的骨标本和MC 3 T3-E1细胞在旋转卸载条件下的水平显着降低。OGRU过表达促进正常负荷条件下成骨细胞活性和基质矿化，并减弱旋转卸载诱导的MC 3 T3-E1细胞分化抑制。此外，该研究发现，通过（DSS）6-脂质体递送到后肢未加载（HLU）小鼠的骨形成表面补充pcDNA3.1（+）-OGRU部分减轻了未加载诱导的骨丢失。机制研究表明，OGRU作为竞争性内源性RNA（ceRNA），通过竞争性结合miR-320- 3 p促进Hoxa 10蛋白表达，从而促进成骨细胞分化和骨形成。总之，我们的研究结果首次澄清了lncRNA OGRU在通过miR-320- 3 p/Hoxa 10轴卸载诱导的骨丢失中的作用，表明骨质疏松症治疗的有效合成代谢策略。
Unloading-induced bone loss is a threat to human health and can eventually result in osteoporotic fractures. Although the underlying molecular mechanism of unloading-induced bone loss has been broadly elucidated, the pathophysiological role of long noncoding RNAs (lncRNAs) in this process is unknown. Here, we identified a novel lncRNA, OGRU, a 1816-nucleotide transcript with significantly decreased levels in bone specimens from hindlimb-unloaded mice and in MC3T3-E1 cells under clinorotation-unloading conditions. OGRU overexpression promoted osteoblast activity and matrix mineralization under normal loading conditions, and attenuated the suppression of MC3T3-E1 cell differentiation induced by clinorotation unloading. Furthermore, this study found that supplementation of pcDNA3.1(+)–OGRU via (DSS)6–liposome delivery to the bone-formation surfaces of hindlimb-unloaded (HLU) mice partially alleviated unloading-induced bone loss. Mechanistic investigations demonstrated that OGRU functions as a competing endogenous RNA (ceRNA) to facilitate the protein expression of Hoxa10 by competitively binding miR-320-3p and subsequently promote osteoblast differentiation and bone formation. Taken together, the results of our study provide the first clarification of the role of lncRNA OGRU in unloading-induced bone loss through the miR-320-3p/Hoxa10 axis, suggesting an efficient anabolic strategy for osteoporosis treatment.