Osthole ameliorates simulated microgravity-induced bone loss through down-regulation of miR-34c-5p
Osthole ameliorates simulated microgravity-induced bone loss through down-regulation of miR-34c-5p
复制标题
蛇床子素通过下调 miR-34c-5p 改善模拟微重力诱导的骨质流失
DOI：
10.1016/j.actaastro.2021.03.015
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发表时间：
2021-03-30
影响因子：
3.5
通讯作者：
Wang, Jufang
中科院分区：
文献类型：
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作者：
Feng, Xiu;Zhou, Heng;Wang, Jufang
骨丢失严重威胁着长期航天飞行中航天员的身体健康，目前所采取的防治措施效果有限。近年来的研究表明，蛇床子素在诱导成骨细胞分化和骨形成中具有积极的作用。本研究以成骨细胞为模型，以随机定位机和后肢去负荷大鼠为实验对象，观察了OST对成骨细胞骨代谢的影响。结果表明，模拟微重力条件下，OST可促进成骨细胞增殖，并提高RUNX 2和BMP 2的表达水平。此外，后肢卸载大鼠给予OST（5 mg/kg/d，i.g.）与用安慰剂（0.9%盐水）处理的大鼠相比，在血清中显示出改善的骨量、骨强度、骨形成标志物（BALP和OCN）的表达以及降低的骨吸收标志物（CTX-1和TRACP-5 b）的表达。值得注意的是，我们发现在体外和体内模拟微重力条件下，miR-34 c-5 p表达水平均显著上调，并且通过抑制miR-34 c-5 p在大鼠中的表达，可以明显挽救模拟微重力引起的骨密度和骨小梁微观结构的损伤。重要的是，OST处理逆转了后肢卸载大鼠中的miR-34 c-5 p表达水平，并且通过转染OST处理的成骨细胞中的agomiR使miR-34 c-5 p的异位表达降低了骨形成基因COL 1 α 1、RUNX 2和BMP 2的表达水平。总的来说，这些数据表明OST通过控制miR-34 c-5 p表达在调节微重力诱导的骨丢失中的未公开作用，这可能有助于对抗太空飞行中骨丢失的发展。
Bone loss severely threatens the heath of astronauts in long-term spaceflight and the effects of the developed countermeasures are limited. Emerging studies have revealed the positive role of osthole (OST) in induction of osteogenic differentiation and bone formation. In this study, the effects of OST on bone metabolism were investigated in osteoblasts and rats treated with random positioning machine and hindlimb unloading, respectively. The results showed that OST treatment promoted the cellular proliferation and elevated the expression levels of RUNX2 and BMP2 in osteoblasts under simulated microgravity. In addition, hindlimb unloading rats administered with OST (5 mg kg/d, i.g.) exhibited improved bone mass, bone strength, expression of bone formation markers (BALP and OCN), and decreased expression of bone resorption markers (CTX-1 and TRACP-5b) in serum compared with rats treated with placebo (0.9% saline). Notably, we found that miR-34c-5p expression level was significantly up-regulated when exposed to simulated microgravity both in vitro and in vivo, and suppression of miR-34c-5p by antagomiR in rats obviously rescued the damages of BMD and trabecular bone microstructures caused by simulated microgravity. Importantly, OST treatment reversed miR-34c-5p expression level in hindlimb unloading rats, and ectopic expression of miR-34c-5p by transfection of agomiR in osteoblasts treated with OST decreased the expression levels of bone formation genes COL1 alpha 1, RUNX2, and BMP2. Overall, these data suggest an undisclosed role for OST in regulating microgravity-induced bone loss via control of miR-34c-5p expression, which may help to countermeasure development to overcome bone loss in spaceflight.