Impairment of 7F2 osteoblast function by simulated partial gravity in a Random Positioning Machine.
Justin Braveboy-WagnerPeter I LelkesPublished in: NPJ microgravity (2022)
The multifaceted adverse effects of reduced gravity pose a significant challenge to human spaceflight. Previous studies have shown that bone formation by osteoblasts decreases under microgravity conditions, both real and simulated. However, the effects of partial gravity on osteoblasts' function are less well understood. Utilizing the software-driven newer version of the Random Positioning Machine (RPM SW ), we simulated levels of partial gravity relevant to future manned space missions: Mars (0.38 G), Moon (0.16 G), and microgravity (Micro, ~10 -3 G). Short-term (6 days) culture yielded a dose-dependent reduction in proliferation and the enzymatic activity of alkaline phosphatase (ALP), while long-term studies (21 days) showed a distinct dose-dependent inhibition of mineralization. By contrast, expression levels of key osteogenic genes (Alkaline phosphatase, Runt-related Transcription Factor 2, Sparc/osteonectin) exhibited a threshold behavior: gene expression was significantly inhibited when the cells were exposed to Mars-simulating partial gravity, and this was not reduced further when the cells were cultured under simulated Moon or microgravity conditions. Our data suggest that impairment of cell function with decreasing simulated gravity levels is graded and that the threshold profile observed for reduced gene expression is distinct from the dose dependence observed for cell proliferation, ALP activity, and mineral deposition. Our study is of relevance, given the dearth of research into the effects of Lunar and Martian gravity for forthcoming space exploration.
Keyphrases
- gene expression
- transcription factor
- induced apoptosis
- endothelial cells
- cell proliferation
- dna methylation
- cell cycle arrest
- signaling pathway
- poor prognosis
- bone marrow
- magnetic resonance
- mesenchymal stem cells
- genome wide
- oxidative stress
- electronic health record
- computed tomography
- cell cycle
- hydrogen peroxide
- current status
- bone regeneration