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.

运动引起的机械负荷可以增加骨骼强度，而机械卸载会增加骨质流失。在这里，我们研究了 lncRNA NONMMUT004552.2 在卸载引起的骨丢失中的作用。在后肢无负载的小鼠中敲除 lncRNA NONMMUT004552.2 导致骨形成和成骨细胞活性增加。 lncRNA NONMMUT004552.2的沉默还减少了MC3T3-E1细胞中成骨细胞的凋亡以及Bax和cleaved caspase-3的表达，增加了Bcl-2蛋白的表达。机制研究表明，NONMMUT004552.2 作为竞争性内源 RNA (ceRNA)，通过竞争性结合 miR-15b-5p 促进含有血影蛋白重复序列​​的核膜 1 (Syne1) 的蛋白表达，随后抑制成骨细胞分化和骨形成。微重力卸载环境。这些数据强调了 lncRNA NONMMUT004552.2/miR-15b-5p/Syne1 轴对于治疗骨质疏松症的重要性。