Mimicking the effects of spaceflight on bone: Combined effects of disuse and chronic low-dose rate radiation exposure on bone mass in mice

Yu, Kanglun; Doherty, Alison H.; Genik, Paula C.; Gookin, Sara E.; Roteliuk, Danielle M.; Wojda, Samantha J.; Jiang, Zhi Sheng; McGee‐Lawrence, Meghan E.; Weil, Michael M.; Donahue, Seth W.

doi:10.1016/j.lssr.2017.08.004

Cited by 19 publications

(12 citation statements)

References 39 publications

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“…Beyond LEO, for example, astronauts may be exposed to up to 0.7 Sv of ionizing radiation 12,15,17 during a multi-year mission to the Moon or Mars 14,15,18 .On Earth, bone homeostasis is effectively maintained by the controlled remodeling activity of bone-forming osteoblasts and bone-resorbing osteoclasts. However, exposure to low-LET radiation ( 137 Cs or X-ray, 1-2 Gy) leads to a transient increase in the number of osteoclasts, accompanied by an increase in trabecular separation (Tb.Sp) and decrease in trabecular thickness (Tb.Th), overall leading to a reduction in bone volume fraction (BV/TV) [19][20][21][22] . Together, this early increase in bone resorption and decrease in bone formation due to radiation exposure can result in a state of osteopenia, potentially leading to an increased risk of bone fracture 16,23,24 .…”

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confidence: 99%

“…Since the spaceflight environment includes exposure to both IR and microgravity, we sought to extend our hypothesis that DP could be a countermeasure for both radiation-and microgravity-induced bone loss. The current literature indicates that simulated microgravity and IR each have detrimental effects on cancellous bone structure, although there is no consensus on whether simulated microgravity and IR cause additive or synergistic effects when combined 20,44,45 . Thus, more studies are needed to determine whether combining simulated microgravity and IR leads to cumulative effects compared to simulated microgravity and IR alone.…”

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Dietary countermeasure mitigates simulated spaceflight-induced osteopenia in mice

Steczina

Tahimic

Pendleton

et al. 2020

Sci Rep

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Spaceflight is a unique environment that includes at least two factors which can negatively impact skeletal health: microgravity and ionizing radiation. We have previously shown that a diet supplemented with dried plum powder (DP) prevented radiation-induced bone loss in mice. In this study, we investigated the capacity of the DP diet to prevent bone loss in mice following exposure to simulated spaceflight, combining microgravity (by hindlimb unloading) and radiation exposure. The DP diet was effective at preventing most decrements in bone micro-architectural and mechanical properties due to hindlimb unloading alone and simulated spaceflight. Furthermore, we show that the DP diet can protect osteoprogenitors from impairments resulting from simulated microgravity. Based on our findings, a dietary supplementation with DP could be an effective countermeasure against the skeletal deficits observed in astronauts during spaceflight.Alterations in the gravity vector and exposure to ionizing radiation can disrupt skeletal homeostasis in mice 1-3 . There are multiple stressors associated with spaceflight, including microgravity and radiation which are known to cause bone loss 4-6 . Decrements in bone mineral density (BMD) have been observed in astronauts from the Mir missions as well as missions to the International Space Station (ISS) 7-9 . While much research has focused on the detrimental effects of microgravity on skeletal tissue, less is known about the impact of spaceflight radiation. Crewed missions have, to this point, primarily remained within low-Earth orbit (LEO). While sources of ionizing space radiation within LEO include galactic cosmic radiation and charged particles from unpredictable solar particle events (SPE) 10,11 , the presence of the Earth's magnetosphere reduces exposure to ionizing space radiation. Missions beyond LEO pose the greatest risk of radiation exposure and is of significant concern for crew health 12-14 . Spaceflight-relevant radiation includes a mix of low-linear energy transfer (LET) species such as protons and helium ions as well as high-LET species such as iron 15,16 . Beyond LEO, for example, astronauts may be exposed to up to 0.7 Sv of ionizing radiation 12,15,17 during a multi-year mission to the Moon or Mars 14,15,18 .On Earth, bone homeostasis is effectively maintained by the controlled remodeling activity of bone-forming osteoblasts and bone-resorbing osteoclasts. However, exposure to low-LET radiation ( 137 Cs or X-ray, 1-2 Gy) leads to a transient increase in the number of osteoclasts, accompanied by an increase in trabecular separation (Tb.Sp) and decrease in trabecular thickness (Tb.Th), overall leading to a reduction in bone volume fraction (BV/TV) [19][20][21][22] . Together, this early increase in bone resorption and decrease in bone formation due to radiation exposure can result in a state of osteopenia, potentially leading to an increased risk of bone fracture 16,23,24 . A possible mechanism of action responsible for these changes in bone homeostasis is the generation o...

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confidence: 99%

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confidence: 99%

Dietary countermeasure mitigates simulated spaceflight-induced osteopenia in mice

Steczina

Tahimic

Pendleton

et al. 2020

Sci Rep

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“…29 A recently published study, unique in delivering 1.7 Gy gamma radiation at very low-dose rates continuously over 20 days to 14-week-old C57/Bl6 female mice, demonstrated no exacerbation of bone structural decrements with concurrent hindlimb unloading. 30 Given that in the current study our high-LET radiation dose was delivered to ambulatory mice on day 1 of the experiment and the G/6 treatment began only 4 days later, it might be that local production of TGF-beta and OPG as observed by Deloch et al in isolated bone/cartilage cells 96 h after irradiation contributed to the positive impacts on bone structure and, possibly, osteoblast function observed in our irradiated mice. 27 Alternatively, it may be that the four days of normal ground reaction forces experienced immediately following high-LET exposure (before the G/6 treatment began) in the current study might have provided enough anabolic stimulus to counteract any early negative impact of an acute radiation exposure on osteoblast activity.…”

Section: Discussionmentioning

confidence: 74%

Positive impact of low-dose, high-energy radiation on bone in partial- and/or full-weightbearing mice

et al. 2019

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Astronauts traveling beyond low Earth orbit will be exposed to galactic cosmic radiation (GCR); understanding how high energy ionizing radiation modifies the bone response to mechanical unloading is important to assuring crew health. To investigate this, we exposed 4-mo-old female Balb/cBYJ mice to an acute space-relevant dose of 0.5 Gy 56 Fe or sham ( n = ~8/group); 4 days later, half of the mice were also subjected to a ground-based analog for 1/6 g (partial weightbearing) (G/6) for 21 days. Microcomputed tomography (µ-CT) of the distal femur reveals that 56 Fe exposure resulted in 65–78% greater volume and improved microarchitecture of cancellous bone after 21 d compared to sham controls. Radiation also leads to significant increases in three measures of energy absorption at the mid-shaft femur and an increase in stiffness of the L4 vertebra. No significant effects of radiation on bone formation indices are detected; however, G/6 leads to reduced % mineralizing surface on the inner mid-tibial bone surface. In separate groups allowed 21 days of weightbearing recovery from G/6 and/or 56 Fe exposure, radiation-exposed mice still exhibit greater bone mass and improved microarchitecture vs. sham control. However, femoral bone energy absorption values are no longer higher in the 56 Fe-exposed WB mice vs. sham controls. We provide evidence for persistent positive impacts of high-LET radiation exposure preceding a period of full or partial weightbearing on bone mass and microarchitecture in the distal femur and, for full weightbearing mice only and more transiently, cortical bone energy absorption values.

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“…Humans on earth are protected from the most harmful space radiation due to the presence of our magnetosphere and the Van Allen belts [ 165 ]; however, astronauts receive a higher dose of solar particles. This radiation exposure to galactic cosmic rays (GCR) is problematic for astronauts on low-Earth orbit space (LEO) missions (e.g., missions carried onboard the ISS), but this exposure may be particularly impactful during long duration missions, such as to the Moon or Mars It has long been known that radiation has deleterious effects on physiological systems [ 69 ] including on the skeletal [ 26 , 67 , 166 , 167 ], muscular [ 168 ], neurological [ 168 , 169 ], immune [ 170 ], and cardiovascular systems [ 96 , 106 , 171 ]. More recent works have begun to establish that radiation and microgravity are associated with a shift in circulating miRNA expression [ 172 ].…”

Section: Outstanding Questionsmentioning

confidence: 99%

Approaching Gravity as a Continuum Using the Rat Partial Weight-Bearing Model

Mortreux

Rosa‐Caldwell

2020

Life

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For decades, scientists have relied on animals to understand the risks and consequences of space travel. Animals remain key to study the physiological alterations during spaceflight and provide crucial information about microgravity-induced changes. While spaceflights may appear common, they remain costly and, coupled with limited cargo areas, do not allow for large sample sizes onboard. In 1979, a model of hindlimb unloading (HU) was successfully created to mimic microgravity and has been used extensively since its creation. Four decades later, the first model of mouse partial weight-bearing (PWB) was developed, aiming at mimicking partial gravity environments. Return to the Lunar surface for astronauts is now imminent and prompted the need for an animal model closer to human physiology; hence in 2018, our laboratory created a new model of PWB for adult rats. In this review, we will focus on the rat model of PWB, from its conception to the current state of knowledge. Additionally, we will address how this new model, used in conjunction with HU, will help implement new paradigms allowing scientists to anticipate the physiological alterations and needs of astronauts. Finally, we will discuss the outstanding questions and future perspectives in space research and propose potential solutions using the rat PWB model.

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Mimicking the effects of spaceflight on bone: Combined effects of disuse and chronic low-dose rate radiation exposure on bone mass in mice

Cited by 19 publications

References 39 publications

Dietary countermeasure mitigates simulated spaceflight-induced osteopenia in mice

Dietary countermeasure mitigates simulated spaceflight-induced osteopenia in mice

Positive impact of low-dose, high-energy radiation on bone in partial- and/or full-weightbearing mice

Approaching Gravity as a Continuum Using the Rat Partial Weight-Bearing Model

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