Global cannabinoid receptor 1 deficiency affects disuse-induced bone loss in a site-specific and sex-dependent manner

DeNapoli, Rachel C.; Buettmann, Evan G.; Friedman, Michael; Lichtman, Aron H.; Donahue, Henry J.

doi:10.1016/j.jbiomech.2022.111414

Cited by 5 publications

(2 citation statements)

References 32 publications

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“…In the future, both males and females should be considered as genetic variation due to sex differences could also influence the skeletal muscle response to microgravity. Indeed, we have found this to be the case in bone response to disuse 109 . Since the strains used in this study are inbred, they do not fully reflect the genetic diversity seen in the DO mice.…”

Section: Discussionmentioning

confidence: 52%

Genetic diversity modulates the physical and transcriptomic response of skeletal muscle to simulated microgravity in male mice

Zeineddine,

Friedman,

Buettmann

et al. 2023

npj Microgravity

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Developments in long-term space exploration necessitate advancements in countermeasures against microgravity-induced skeletal muscle loss. Astronaut data shows considerable variation in muscle loss in response to microgravity. Previous experiments suggest that genetic background influences the skeletal muscle response to unloading, but no in-depth analysis of genetic expression has been performed. Here, we placed eight, male, inbred founder strains of the diversity outbred mice (129S1/SvImJ, A/J, C57BL/6J, CAST/EiJ, NOD/ShiLtJ, NZO/HILtJ, PWK/PhJ, and WSB/EiJ) in simulated microgravity (SM) via hindlimb unloading for three weeks. Body weight, muscle morphology, muscle strength, protein synthesis marker expression, and RNA expression were collected. A/J and CAST/EiJ mice were most susceptible to SM-induced muscle loss, whereas NOD/ShiLtJ mice were the most protected. In response to SM, A/J and CAST/EiJ mice experienced reductions in body weight, muscle mass, muscle volume, and muscle cross-sectional area. A/J mice had the highest number of differentially expressed genes (68) and associated gene ontologies (328). Downregulation of immunological gene ontologies and genes encoding anabolic immune factors suggest that immune dysregulation contributes to the response of A/J mice to SM. Several muscle properties showed significant interactions between SM and mouse strain and a high degree of heritability. These data imply that genetic background plays a role in the degree of muscle loss in SM and that more individualized programs should be developed for astronauts to protect their skeletal muscles against microgravity on long-term missions.

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Section: Discussionmentioning

confidence: 52%

Genetic diversity modulates the physical and transcriptomic response of skeletal muscle to simulated microgravity in male mice

Zeineddine,

Friedman,

Buettmann

et al. 2023

npj Microgravity

Self Cite

View full text Add to dashboard Cite

show abstract

“…Indeed, we have found this to be the case in bone response to disuse. 108 Since the strains used in this study are inbred, they do not fully reflect the genetic diversity seen in the DO mice. Exploring how SM affects DO mice will be necessary to better understand the role of genetic variation and discover causal genes regulating the skeletal muscle response to SM.…”

Section: Discussionmentioning

confidence: 99%

Genetic Diversity Modulates The Physical And Transcriptomic Response Of Skeletal Muscle To Simulated Microgravity

Zeineddine

Friedman

Buettmann

et al. 2023

Preprint

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Developments in long-term space exploration necessitate advancements in countermeasures against microgravity-induced skeletal muscle loss. Astronaut data shows considerable variation in muscle loss in response to microgravity. Previous experiments suggest that genetic background influences the skeletal muscle response to unloading, but no in-depth analysis of genetic expression was performed. Here, we placed eight inbred founder strains of the diversity outbred mice (129S1/SvImJ, A/J, C57BL/6J, CAST/EiJ, NOD/ShiLtJ, NZO/HILtJ, PWK/PhJ, and WSB/EiJ) in simulated microgravity (SM) via hindlimb unloading for three weeks. Body weight, muscle morphology, muscle strength, protein synthesis marker expression, and RNA expression were collected. A/J and CAST/EiJ mice were most susceptible to SM-induced muscle loss, whereas NOD/ShiLtJ mice were the most protected. In response to SM, A/J and CAST/EiJ mice experienced reductions in body weight, muscle mass, muscle volume, and muscle cross-sectional area. A/J mice had the highest number of differentially expressed genes (68) and associated gene ontologies (328). Downregulation of immunological gene ontologies and genes encoding anabolic immune factors suggest that immune dysregulation contributes to the response of A/J mice to SM. Several muscle properties showed significant interactions between SM and mouse strain and a high degree of heritability. These data imply that genetic background plays a role in the degree of muscle loss in SM and that more individualized programs should be developed for astronauts to protect their skeletal muscles against microgravity on long term missions.

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Reambulation following hindlimb unloading attenuates disuse-induced changes in murine fracture healing

Buettmann

DeNapoli

Abraham

et al. 2023

Bone

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Global cannabinoid receptor 1 deficiency affects disuse-induced bone loss in a site-specific and sex-dependent manner

Cited by 5 publications

References 32 publications

Genetic diversity modulates the physical and transcriptomic response of skeletal muscle to simulated microgravity in male mice

Genetic diversity modulates the physical and transcriptomic response of skeletal muscle to simulated microgravity in male mice

Genetic Diversity Modulates The Physical And Transcriptomic Response Of Skeletal Muscle To Simulated Microgravity

Reambulation following hindlimb unloading attenuates disuse-induced changes in murine fracture healing

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