Global transcriptomic analysis of a murine osteocytic cell line subjected to spaceflight.
International Space Station
bone cells
bone loss
gene expression
microgravity
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
13
03
2021
received:
13
01
2021
accepted:
22
03
2021
entrez:
9
4
2021
pubmed:
10
4
2021
medline:
20
7
2021
Statut:
ppublish
Résumé
Bone loss is a major health concern for astronauts during long-term spaceflight and for patients during prolonged bed rest or paralysis. Growing evidence suggests that osteocytes, the most abundant cells in the mineralized bone matrix, play a key role in sensing mechanical forces applied to the skeleton and integrating the orchestrated response into subcellular biochemical signals to modulate bone homeostasis. However, the precise molecular mechanisms underlying both mechanosensation and mechanotransduction in late-osteoblast-to-osteocyte cells under microgravity (µG) have yet to be elucidated. To unravel the mechanisms by which late osteoblasts and osteocytes sense and respond to mechanical unloading, we exposed the osteocytic cell line, Ocy454, to 2, 4, or 6 days of µG on the SpaceX Dragon-6 resupply mission to the International Space Station. Our results showed that µG impairs the differentiation of osteocytes, consistent with prior osteoblast spaceflight experiments, which resulted in the downregulation of key osteocytic genes. Importantly, we demonstrate the modulation of critical glycolysis pathways in osteocytes subjected to microgravity and discovered a set of mechanical sensitive genes that are consistently regulated in multiple cell types exposed to microgravity suggesting a common, yet to be fully elucidated, genome-wide response to microgravity. Ground-based simulated microgravity experiments utilizing the NASA rotating-wall-vessel were unable to adequately replicate the changes in microgravity exposure highlighting the importance of spaceflight missions to understand the unique environmental stress that microgravity presents to diverse cell types. In summary, our findings demonstrate that osteocytes respond to µG with an increase in glucose metabolism and oxygen consumption.
Identifiants
pubmed: 33835498
doi: 10.1096/fj.202100059R
doi:
Substances chimiques
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21578Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR059741
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR059655
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH3 AR059655
Pays : United States
Organisme : NCATS NIH HHS
ID : U54 TR001012
Pays : United States
Informations de copyright
© 2021 Federation of American Societies for Experimental Biology.
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