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Dexamethasone-induced muscle atrophy and bone loss in six genetically diverse collaborative cross founder strains demonstrates phenotypic variability by Rg3 treatment

  • Bao Ngoc Nguyen (College of Dentistry, Gangneung Wonju National University) ;
  • Soyeon Hong (Convergence Research Center for Smart Farm Solution, Korea Institute of Science and Technology (KIST)) ;
  • Sowoon Choi (Natural Product Research Center, Korea Institute of Science and Technology (KIST)) ;
  • Choong-Gu Lee (Natural Product Informatics Research Center, Korea Institute of Science and Technology (KIST)) ;
  • GyHye Yoo (Convergence Research Center for Smart Farm Solution, Korea Institute of Science and Technology (KIST)) ;
  • Myungsuk Kim (Natural Product Research Center, Korea Institute of Science and Technology (KIST))
  • 투고 : 2023.05.24
  • 심사 : 2023.12.26
  • 발행 : 2024.05.01

초록

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.

키워드

과제정보

This research was supported by Korea Institute of Science and Technology intramural research grants and grant from the National Research Foundation of Korea (2021R1C1C1007040).

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