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Mechanical loading of tissue engineered skeletal muscle prevents dexamethasone induced myotube atrophy

Aguilar-Agon, KW; Capel, AJ; Fleming, JW; Player, DJ; Martin, NRW; Lewis, MP; (2020) Mechanical loading of tissue engineered skeletal muscle prevents dexamethasone induced myotube atrophy. Journal of Muscle Research and Cell Motility 10.1007/s10974-020-09589-0. (In press). Green open access

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Abstract

Skeletal muscle atrophy as a consequence of acute and chronic illness, immobilisation, muscular dystrophies and aging, leads to severe muscle weakness, inactivity and increased mortality. Mechanical loading is thought to be the primary driver for skeletal muscle hypertrophy, however the extent to which mechanical loading can offset muscle catabolism has not been thoroughly explored. In vitro 3D-models of skeletal muscle provide a controllable, high throughput environment and mitigating many of the ethical and methodological constraints present during in vivo experimentation. This work aimed to determine if mechanical loading would offset dexamethasone (DEX) induced skeletal muscle atrophy, in muscle engineered using the C2C12 murine cell line. Mechanical loading successfully offset myotube atrophy and functional degeneration associated with DEX regardless of whether the loading occurred before or after 24 h of DEX treatment. Furthermore, mechanical load prevented increases in MuRF-1 and MAFbx mRNA expression, critical regulators of muscle atrophy. Overall, we demonstrate the application of tissue engineered muscle to study skeletal muscle health and disease, offering great potential for future use to better understand treatment modalities for skeletal muscle atrophy.

Type: Article
Title: Mechanical loading of tissue engineered skeletal muscle prevents dexamethasone induced myotube atrophy
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s10974-020-09589-0
Publisher version: https://doi.org/10.1007/s10974-020-09589-0
Language: English
Additional information: © 2020 Springer Nature Switzerland AG. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
Keywords: C2C12, Dexamethasone, Hypertrophy, Myotubes, Skeletal muscle, Ubiquitin–proteasome
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Ortho and MSK Science
URI: https://discovery.ucl.ac.uk/id/eprint/10111148
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