(D-160) Simulated Microgravity Accurately Models Spaceflight Effects on Bone and Muscle in Skeletally Immature Mice

Mechanical unloading, whether from prolonged disuse or spaceflight, has been shown to have detrimental effects on bone and muscle health, leading to a decrease in volume and an increased risk of fractures..1 In animal studies, hindlimb unloading has emerged as the most commonly used model to simulate the effects of unloading on musculoskeletal tissues. However, a direct comparison between hindlimb unloading and spaceflight has yet to be conducted. The effects of hindlimb unloading and spaceflight on bone and muscle have been primarily investigated using male C57BL/6 mice, and the duration of these studies typically ranges from 2 to 3 weeks.2 While these studies have provided valuable insights, there is a need to explore the effects of longer-duration spaceflight, especially in consideration of future missions to the moon and Mars, which will involve diverse crews and extended stays in space. This study aims to examine the effects of 6 weeks of spaceflight in female Balb/c mice from the Rodent Research Reference Mission-1. By utilizing female mice and extending the duration of spaceflight, this study aims to provide a more comprehensive understanding of the impact of long-duration space missions on musculoskeletal health. Furthermore, the study hypothesizes that hindlimb unloading, a well-established model, accurately simulates the physiological changes observed during extended spaceflight in these mice. By comparing the effects of spaceflight and hindlimb unloading, this study aimed to provide valuable insights into the applicability of hindlimb unloading as a model for simulating the effects of long-duration spaceflight on musculoskeletal health.

In spaceflight, the absence of gravity leads to a unique set of physiological challenges for astronauts, including musculoskeletal changes. Typically, prolonged space missions cause muscle atrophy, decreased bone density, and alterations in gene and protein expression.3 This study compared hindlimb unloading and spaceflight to study their effects on gene expression. As shown in Figure 1, FBxo32 gene expression, which is responsible for muscle atrophy, was decreased in hindlimb unloading while other genes demonstrated little or no significant decrease for hindlimb unloading. These were unexpected findings, as spaceflight typically increases muscle atrophy. One plausible explanation is that muscles adapt to the microgravity environment over time and reach a state of homeostasis, which might have been achieved by the time gene expression was measured.2,3 These results diverged from the norm, possibly due to the study's specific conditions, such as long mission duration, or use of different mouse strain. The knowledge gained from this experiment is crucial for long-duration spaceflight. Understanding how muscles adapt and maintain homeostasis in microgravity can help in developing effective countermeasures to mitigate musculoskeletal issues faced by astronauts. By examining gene expression changes at early time points, researchers can identify potential targets for interventions that promote muscle preservation during space missions. In the future, we will analyze changes in protein expression in the gastrocnemius muscle. Analyzing the change in protein expression for the gastrocnemius muscle will offer insights into the functional consequences of gene regulation. Ultimately, this research contributes to the development of personalized and targeted strategies to ensure astronauts' health and performance during extended space missions, thereby advancing humanity's prospects for future exploration beyond Earth's boundaries.

1. 
   

   Lang et al., NPJ Microgravity 2017

   
   


2. 
   

   Coulombe et al., Bone 2021

   
   


3. 
   

   Lang et al., J Bone Miner Res 2009