Wubshet Nadab H, Cai Grace, Chen Samuel J, Sullivan Molly, Reeves Mark, Mays David, Harrison Morgan, Varnado Paul, Yang Benjamin, Arreguin-Martinez Esmeralda, Qu Yunjia, Lin Shan-Shan, Duran Pamela, Aguilar Carlos, Giza Shelby, Clements Twyman, Liu Allen P
Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
Applied Physics Program, University of Michigan, Ann Arbor, MI, 48109, USA.
NPJ Microgravity. 2024 Mar 21;10(1):35. doi: 10.1038/s41526-024-00386-4.
Astronauts experience significant and rapid bone loss as a result of an extended stay in space, making the International Space Station (ISS) the perfect laboratory for studying osteoporosis due to the accelerated nature of bone loss on the ISS. This prompts the question, how does the lack of load due to zero-gravity propagate to bone-forming cells, human fetal osteoblasts (hFOBs), altering their maturation to mineralization? Here, we aim to study the mechanotransduction mechanisms by which bone loss occurs in microgravity. Two automated experiments, microfluidic chips capable of measuring single-cell mechanics via aspiration and cell spheroids incubated in pressure-controlled chambers, were each integrated into a CubeLab deployed to the ISS National Laboratory. For the first experiment, we report protrusion measurements of aspirated cells after exposure to microgravity at the ISS and compare these results to ground control conducted inside the CubeLab. We found slightly elongated protrusions for space samples compared to ground samples indicating softening of hFOB cells in microgravity. In the second experiment, we encapsulated osteoblast spheroids in collagen gel and incubated the samples in pressure-controlled chambers. We found that microgravity significantly reduced filamentous actin levels in the hFOB spheroids. When subjected to pressure, the spheroids exhibited increased pSMAD1/5/9 expression, regardless of the microgravity condition. Moreover, microgravity reduced YAP expression, while pressure increased YAP levels, thus restoring YAP expression for spheroids in microgravity. Our study provides insights into the influence of microgravity on the mechanical properties of bone cells and the impact of compressive pressure on cell signaling in space.
由于在太空长期停留，宇航员会经历显著且快速的骨质流失，这使得国际空间站（ISS）成为研究骨质疏松症的理想实验室，因为在国际空间站上骨质流失的速度加快。这就引发了一个问题，即零重力导致的负荷缺失是如何传导至成骨细胞——人类胎儿成骨细胞（hFOB），从而改变其成熟至矿化过程的？在这里，我们旨在研究微重力环境下骨质流失发生的机械转导机制。两项自动化实验，即能够通过抽吸测量单细胞力学的微流控芯片以及在压力控制室内培养的细胞球体，分别被集成到部署到国际空间站国家实验室的CubeLab中。对于第一个实验，我们报告了在国际空间站暴露于微重力环境后抽吸细胞的突起测量结果，并将这些结果与在CubeLab内进行的地面对照结果进行比较。我们发现，与地面样本相比，太空样本的突起略有伸长，这表明微重力环境下hFOB细胞变软。在第二个实验中，我们将成骨细胞球体包裹在胶原蛋白凝胶中，并在压力控制室内培养这些样本。我们发现微重力显著降低了hFOB球体中的丝状肌动蛋白水平。当受到压力时，无论微重力条件如何，球体均表现出pSMAD1/5/9表达增加。此外，微重力降低了YAP表达，而压力增加了YAP水平，从而恢复了微重力环境下球体的YAP表达。我们的研究深入了解了微重力对骨细胞力学性能的影响以及压缩压力对太空细胞信号传导的影响。
