Reducing the bone deterioration that astronauts experience in microgravity requires countermeasures that can improve the effectiveness of rigorous and time-expensive exercise regimens under microgravity. The ability of low intensity vibrations (LIV) to activate force-responsive signaling pathways in cells suggests LIV as a potential countermeasure to improve cell responsiveness to subsequent mechanical challenge. Mechanoresponse of mesenchymal stem cells (MSC) which maintain bone-making osteoblasts is in part controlled by the mechanotransducer protein YAP (Yes-associated protein) which is shuttled into the nucleus in response cyto-mechanical forces. Here, using YAP nuclear shuttling as a measure of MSC mechanoresponse, we tested the effect of 72 hours of simulated microgravity (SMG) and daily LIV application (LIVDT) on the YAP nuclear entry driven by either acute LIV (LIVAT) or Lysophosphohaditic acid (LPA), applied at the end of the 72h period. We hypothesized that SMG-induced impairment of acute YAP nuclear entry will be alleviated by daily application of LIVDT. Results showed that while both acute LIVAT and LPA treatments increased nuclear YAP entry by 50% and 87% over the basal levels in SMG-treated MSCs, nuclear YAP levels of all SMG groups were significantly lower than non-SMG controls. Daily dosing of LIVDT, applied in parallel to SMG, restored the SMG-driven decrease in basal nuclear YAP to control levels as well as increased the LPA-induced but not LIVAT-induced YAP nuclear entry over the non-LIVDT treated, SMG only, counterparts. These cell level observations suggest that utilizing daily LIV treatments is a feasible countermeasure for increasing the YAP-mediated anabolic responsiveness of MSCs to subsequent mechanical challenge under SMG.

中文翻译：

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低强度振动恢复间质干细胞受模拟微重力作用下的核YAP水平和急性YAP核穿梭。

减少宇航员在微重力中经历的骨骼退化，需要采取对策，以提高在微重力下进行严格且费时的运动方案的有效性。低强度振动（LIV）激活细胞中力响应信号通路的能力表明LIV是提高细胞对后续机械挑战的响应能力的潜在对策。维持造骨成骨细胞的间充质干细胞（MSC）的机械反应部分受机械转导蛋白YAP（Yes相关蛋白）控制，该蛋白在响应细胞机械力的作用下穿入细胞核。在这里，使用YAP核穿梭作为MSC机械响应的量度，我们测试了72小时模拟微重力（SMG）和每日LIV施用（LIVDT）对在72h周期结束时应用的急性LIV（LIVAT）或溶血磷酸乙二酸（LPA）驱动的YAP核进入的影响。我们假设每天使用LIVDT可以减轻SMG诱导的急性YAP核进入的损害。结果表明，尽管急性LIVAT和LPA治疗均使SMG治疗的MSC的核YAP进入率较基础水平提高了50％和87％，但所有SMG组的核YAP水平均显着低于非SMG对照组。与SMG并行使用的LIVDT的每日剂量可将SMG驱动的基础核YAP降低恢复至控制水平，并且与未使用LIVDT治疗（仅SMG）相比，LPA诱导的但不是LIVAT诱导的YAP核进入增加。同行。