Astronauts may develop bone loss in space as a result of environmental challenges such as exposure to weightlessness and ionizing radiation. Oxidative stress results from an imbalance between production of free radicals and the ability of cells to counteract their harmful effects at the molecular level. To date, little is known about the combined effects of weightlessness and space radiation on the musculoskeletal system, the cardiovascular system, and how these two systems interact in maintaining bone health. The overall objectives of this study were to define mechanisms and risks of bone loss in space, to explore the relationship between microvessel function and bone loss due to weightlessness and radiation exposure, and to help develop effective ways to prevent bone loss.
This study had the following specific aims:
- Determine the functional and structural consequences of prolonged weightlessness and space radiation (simulated spaceflight) for bone and skeletal vasculature in the context of bone cell function and oxidative stress.
- Determine the extent to which an anti-oxidant protects against weightlessness and space radiation-induced bone loss and vascular dysfunction.
- Determine how low dose space radiation influences later skeletal recovery from prolonged weightlessness.
- Determine if transient treatment with countermeasures protects from bone loss caused by weightlessness and radiation during subsequent aging.
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16-weeks old, male mice were exposed to low linear-energy-transfer (LET) protons or high-LET 56Fe ions using either low or high doses of radiation at NASA’s Space Radiation Lab. Five weeks or one year after irradiation, tissues were harvested and analyzed by microcomputed tomography for cancellous microarchitecture and cortical geometry. Marrow-derived, adherent cells were grown under osteoblastogenic culture conditions.
Investigators discovered that simulated weightlessness causes decrements in both slow-turnover cortical bone tissue and high turnover cancellous tissue, whereas ionization radiation (0.5-2Gy) causes decrements only in cancellous tissue. Whereas the radiation-induced deficits in skeletal microarchitecture diminish over a period of six to seven months due to age-related bone loss in control animals, dysfunction in cell populations persists. HZE but not protons or gamma cause defects in osteoblastogenesis from bone marrow derived stem cells and progenitors. This defect can be attributed to persistent deficits in progenitor cell proliferation and colony growth, whereas the capacity to differentiate into osteoblast-like cells and mineralize an extracellular matrix (the hallmark of osteoblasts) is retained.
In addition, bones from HZE-irradiated animals can respond later to anabolic loading stimulus with improved bone formation, although there is some evidence from analyses by dynamic histomorphometry and gene expression that there may be persistent defects in osteoprogenitor cell populations localized to regions adjacent to the periosteal surfaces of bone tissue. Together, these findings on marrow-derived progenitors and periosteal cell behavior lead investigators to predict that fracture healing and perhaps other wound healing processes that depend mesenchymal stem cells derived from the marrow and/or periosteal bone surfaces are deficient after exposure to HZE at space relevant doses. This prediction is both consistent with a few reports in the scientific literature and may have relevance to regenerative medicine in space, thus represents a potentially important area for future study. With respect to prevention, either mechanical stimulation (resembling vigorous exercise) or feeding a diet containing dried plum, can improve bone structure despite prior exposure to HZE. In contrast, treatment with antioxidants that have displayed at least some radioprotective properties (lipoic acid injections, anti-oxidant cocktail, or treatment with an anti-inflammatory (Ibuprofen)) failed to prevent radiation-induced bone loss. These findings imply treatment with antioxidants alone are unlikely to prove fully protective to the skeleton exposed to ionizing radiation.
Schreurs AS, Shirazi-Fard Y, Shahnazari M, Alwood JS, Truong TA, Tahimic CG, Limoli CL, Turner ND, Halloran B, Globus RK. Dried plum diet protects from bone loss caused by ionizing radiation.
2016. February 11;6:21343. [DOI]
Shirazi-Fard Y, Alwood JS, Schreurs AS, Castillo AB, and Globus RK. Mechanical loading causes site-specific anabolic effects on bone following exposure to ionizing radiation. Bone.
2015. July 18. [DOI]
Alwood, J. S., Shahnazari, M., Chicana, B., Schreurs, A. S., Kumar, A., Bartolini, A., Globus, R. K. (2015). Ionizing Radiation Stimulates Expression of Pro-Osteoclastogenic Genes in Marrow and Skeletal Tissue. Journal of Interferon and Cytokine Research, 35(6), 480–487. [DOI]
Tahimic CGT, Globus RK. Redox signaling and its impact on skeletal and vascular responses to spaceflight. International Journal of Molecular Sciences.
2017 Oct 16;18(10):E2153. [DOI]
Alwood JS, Tran LH, Schreurs AS, Shirazi-Fard Y, Kumar A, Hilton D, Tahimic CGT, and Globus RK. Dose- and ion-dependent effects in the oxidative stress response to space-like radiation exposure in the skeletal system. International Journal of Molecular Sciences.
2017. October 10; 18(10):E2117. [DOI]
Ghosh P, Behnke BJ, Stabley JN, Kilar CR, Park Y, Narayanan A, Alwood JS, Shirazi-Fard Y, Schreurs AS, Globus RK, and Delp MD. Effects of high-LET radiation exposure and hindlimb unloading on skeletal muscle resistance artery vasomotor properties and cancellous bone microarchitecture in mice. Radiation Research.
2016. March; 185(3):257-66. [DOI]
Crew health and performance is critical to successful human exploration beyond low Earth orbit.
The Human Research Program (HRP) investigates and mitigates the highest risks to human health
and performance, providing essential countermeasures and technologies for human space exploration.
Risks include physiological and performance effects from hazards such as radiation, altered gravity,
and hostile environments, as well as unique challenges in medical support, human factors,
and behavioral health support. The HRP utilizes an Integrated Research Plan (IRP) to identify
the approach and research activities planned to address these risks, which are assigned to specific
Elements within the program. The Human Research Roadmap is the web-based tool for communicating the IRP content.
The Human Research Roadmap is located at: https://humanresearchroadmap.nasa.gov/
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for information of how this experiment is contributing to the HRP's path for risk reduction.