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Dexamethasone-induced muscle atrophy and bone loss in six genetically diverse collaborative cross founder strains
Bao Ngoc Nguyen1,2, Soyeon Hong3, Sowoon Choi2
1College of Dentistry, Gangneung Wonju National University, Gangneung, Gangwon-do, Republic of Korea.
Background:
Osteosarcopenia is a common condition characterized by the loss of both bone and muscle mass, which can lead to an increased risk of fractures and disability in older adults. The study aimed to elucidate the response of various mouse strains to treatment with Rg3, one of the leading ginsenosides, on musculoskeletal traits and immune function, and their correlation.
Methods:
Six Collaborative Cross (CC) founder strains induced muscle atrophy and bone loss with dexamethasone (15 mg/kg) treatment for 1 month, and half of the mice for each strain were orally administered Rg3 (20 mg/kg). Different responses were observed depending on genetic background and Rg3 treatment.
Results:
Rg3 significantly increased grip strength, running performance, and expression of muscle and bone health-related genes in a two-way analysis of variance considering the genetic backgrounds and Rg3 treatment. Significant improvements in grip strength, running performance, bone area, and muscle mass, and the increased gene expression were observed in specific strains of PWK/PhJ. For traits related to muscle, bone, and immune functions, significant correlations between traits were confirmed following Rg3 administration compared with control mice. The phenotyping analysis was compiled into a public web resource called Rg3-OsteoSarco.
Conclusion:
This highlights the complex interplay between genetic determinants, pathogenesis of muscle atrophy and bone loss, and phytochemical bioactivity and the need to move away from single inbred mouse models to improve their translatability to genetically diverse humans. Rg3-OsteoSarco highlights the use of CC founder strains as a valuable tool in the field of personalized nutrition.
Insights
Ginsenoside Rg3 improved bone and muscle health in mice with osteosarcopenia, showing strain-specific benefits and correlations with immune function. This highlights Rg3
Area of Science:
- Pharmacology
- Genetics
- Gerontology
Background:
- Osteosarcopenia, characterized by bone and muscle mass loss, increases fracture and disability risks in older adults.
- Understanding the impact of phytochemicals like Rg3 on osteosarcopenia is crucial for developing targeted interventions.
- Genetic diversity influences responses to disease and treatment, necessitating studies using varied genetic models.
Purpose of the Study:
- To investigate the effects of Rg3, a ginsenoside, on musculoskeletal traits and immune function in different mouse strains.
- To explore the correlation between Rg3 treatment, genetic background, and osteosarcopenia-related parameters.
- To establish a public web resource (Rg3-OsteoSarco) for phenotyping data.
Main Methods:
- Six Collaborative Cross (CC) founder mouse strains were induced with muscle atrophy and bone loss using dexamethasone.
- Mice received either Rg3 treatment (20 mg/kg) or a control, with half of each strain treated.
- Musculoskeletal traits, gene expression, and immune function were assessed, with data analyzed using two-way ANOVA.
Main Results:
- Rg3 significantly enhanced grip strength, running performance, and expression of muscle/bone health genes across strains.
- Specific improvements in strength, performance, bone area, muscle mass, and gene expression were noted in PWK/PhJ mice.
- Significant correlations between muscle, bone, and immune functions were observed post-Rg3 administration.
Conclusions:
- Genetic background critically influences the response to Rg3 in osteosarcopenia models.
- Rg3 demonstrates potential as a therapeutic agent for age-related bone and muscle loss.
- Collaborative Cross founder strains are valuable for personalized nutrition research, moving beyond single inbred models.
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