Cellular mechanotransduction of human osteoblasts in microgravity.

Autor:	Wubshet NH; Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA., Cai G; Applied Physics Program, University of Michigan, Ann Arbor, MI, USA., Chen SJ; Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA., Sullivan M; Space Tango, Lexington, KY, USA., Reeves M; Space Tango, Lexington, KY, USA., Mays D; Space Tango, Lexington, KY, USA., Harrison M; Space Tango, Lexington, KY, USA., Varnado P; Space Tango, Lexington, KY, USA., Yang B; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA., Arreguin-Martinez E; Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA., Qu Y; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA., Lin SS; Applied Physics Program, University of Michigan, Ann Arbor, MI, USA., Duran P; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA., Aguilar C; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA., Giza S; Space Tango, Lexington, KY, USA., Clements T; Space Tango, Lexington, KY, USA., Liu AP; Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA.; Applied Physics Program, University of Michigan, Ann Arbor, MI, USA.; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.; Department of Biophysics, University of Michigan, Ann Arbor, MI, USA.; Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Mar 03. Date of Electronic Publication: 2024 Mar 03.
DOI:	10.1101/2024.03.03.583164
Abstrakt:	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, 4 microfluidic chips capable of measuring single-cell mechanics of hFOBs 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. Our analysis revealed 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 behavior and signaling in space. Competing Interests: COMPETING INTERESTS The authors declare no competing interests.
Databáze:	MEDLINE
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