Zhang Zheng, Jing Yu, Zhang Ang, Liu JiShan, Yang Heming, Lou Xiaotong, Xu Liyan, Liu Min, Zhang Yikun, Gu Jianwen
Department of Medical Engineering, PLA Strategic Support Force Characteristic Medical Center, Beijing, 100101, China.
Department of Haematology, The Fifth Medical Centre of Chinese PLA General Hospital, Beijing, 100071, China.
NPJ Microgravity. 2024 Mar 23;10(1):37. doi: 10.1038/s41526-024-00382-8.
Exercise-induced mechanical loading can increase bone strength whilst mechanical unloading enhances bone-loss. Here, we investigated the role of lncRNA NONMMUT004552.2 in unloading-induced bone-loss. Knockout of lncRNA NONMMUT004552.2 in hindlimb-unloaded mice caused an increase in the bone formation and osteoblast activity. The silencing of lncRNA NONMMUT004552.2 also decreased the osteoblast apoptosis and expression of Bax and cleaved caspase-3, increased Bcl-2 protein expression in MC3T3-E1 cells. Mechanistic investigations demonstrated that NONMMUT004552.2 functions as a competing endogenous RNA (ceRNA) to facilitate the protein expression of spectrin repeat containing, nuclear envelope 1 (Syne1) by competitively binding miR-15b-5p and subsequently inhibits the osteoblast differentiation and bone formation in the microgravity unloading environment. These data highlight the importance of the lncRNA NONMMUT004552.2/miR-15b-5p/Syne1 axis for the treatment of osteoporosis.
运动诱导的机械负荷可增强骨强度，而机械卸载则会加剧骨质流失。在此，我们研究了lncRNA NONMMUT004552.2在卸载诱导的骨质流失中的作用。敲除后肢卸载小鼠中的lncRNA NONMMUT004552.2会导致骨形成和成骨细胞活性增加。lncRNA NONMMUT004552.2的沉默还减少了成骨细胞凋亡以及Bax和裂解的caspase-3的表达，增加了MC3T3-E1细胞中Bcl-2蛋白的表达。机制研究表明，NONMMUT004552.2作为一种竞争性内源RNA（ceRNA），通过竞争性结合miR-15b-5p来促进含血影蛋白重复序列的核膜蛋白1（Syne1）的蛋白表达，进而在微重力卸载环境中抑制成骨细胞分化和骨形成。这些数据突出了lncRNA NONMMUT004552.2/miR-15b-5p/Syne1轴在骨质疏松症治疗中的重要性。
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