ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2020
Gene-Metabolite Network Linked to Inhibited Bioenergetics in Association With Spaceflight-Induced Loss of Male Mouse Quadriceps Muscle.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- NSAIDs trigger drug-specific response to exercise: a multi-omics systems biology analysis of a randomized crossover trial.Skeletal muscle · 2026Trial
- Simulated Microgravity Induced Mesenchymal Stem Cell Senescence via the Activation of Cytosolic mtDNA-cGAS-STING Axis.Journal of cellular physiology · 2026Article
- Spaceflight exposome/microgravity effects on the psychoimmunoneuroendocrine system.NPJ microgravity · 2025Review
- Oxidative Stress on the Ground and in the Microgravity Environment: Pathophysiological Effects and Treatment.Antioxidants (Basel, Switzerland) · 2025Review
- Using single-sample networks to identify the contrasting patterns of gene interactions and reveal the radiation dose-dependent effects in multiple tissues of spaceflight mice.NPJ microgravity · 2024Article
- Microgravity's effects on miRNA-mRNA regulatory networks in a mouse model of segmental bone defects.PloS one · 2024Article
- Early to sustained impacts of lethal radiation on circulating miRNAs in a minipig model.Scientific reports · 2023Article
- Meeting report of the sixth annual tri-service microbiome consortium symposium.Environmental microbiome · 2023Article
- VGLL2-NCOA2 leverages developmental programs for pediatric sarcomagenesis.Cell reports · 2023Article
- Alternative splicing diversifies the skeletal muscle transcriptome during prolonged spaceflight.Skeletal muscle · 2022Article
- Biomanufacturing in low Earth orbit for regenerative medicine.Stem cell reports · 2022Review
- Metabolomics as an Important Tool for Determining the Mechanisms of Human Skeletal Muscle Deconditioning.International journal of molecular sciences · 2021Review
- Methodology, selection, and integration of fracture healing assessments in mice.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2021Review
- Spaceflight Modulates the Expression of Key Oxidative Stress and Cell Cycle Related Genes in Heart.International journal of molecular sciences · 2021Article
- Gene-metabolite networks associated with impediment of bone fracture repair in spaceflight.Computational and structural biotechnology journal · 2021Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
Prolonged residence of mice in spaceflight is a scientifically robust and ethically ratified model of muscle atrophy caused by continued unloading. Under the Rodent Research Program of the National Aeronautics and Space Administration (NASA), we assayed the large-scale mRNA and metabolomic perturbations in the quadriceps of C57BL/6j male mice that lived in spaceflight (FLT) or on the ground (control or CTR) for approximately 4 weeks. The wet weights of the quadriceps were significantly reduced in FLT mice. Next-generation sequencing and untargeted mass spectroscopic assays interrogated the gene-metabolite landscape of the quadriceps. A majority of top-ranked differentially suppressed genes in FLT encoded proteins from the myosin or troponin families, suggesting sarcomere alterations in space. Significantly enriched gene-metabolite networks were found linked to sarcomeric integrity, immune fitness, and oxidative stress response; all inhibited in space as per in silico prediction. A significant loss of mitochondrial DNA copy numbers in FLT mice underlined the energy deprivation associated with spaceflight-induced stress. This hypothesis was reinforced by the transcriptomic sequencing-metabolomics integrative analysis that showed inhibited networks related to protein, lipid, and carbohydrate metabolism, and adenosine triphosphate (ATP) synthesis and hydrolysis. Finally, we discovered important upstream regulators, which could be targeted for next-generation therapeutic intervention for chronic disuse of the musculoskeletal system. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
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