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

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journal contribution
posted on 13.08.2021, 12:55 by Kathryn Aguilar-Agon, Andrew CapelAndrew Capel, Jacob Fleming, Darren J. Player, Neil MartinNeil Martin, Mark LewisMark Lewis
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.

Funding

Towards Bespoke Bio-Hybrid Prosthesis - Manufacturing bio-inductive interfaces in 3D

Engineering and Physical Sciences Research Council

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History

School

  • Sport, Exercise and Health Sciences

Published in

Journal of Muscle Research and Cell Motility

Volume

42

Pages

149-159

Publisher

Springer (part of Springer Nature)

Version

VoR (Version of Record)

Rights holder

© The Authors

Publisher statement

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Acceptance date

04/09/2020

Publication date

2020-09-21

Copyright date

2020

ISSN

0142-4319

eISSN

1573-2657

Language

en

Depositor

Dr Andrew Capel. Deposit date: 16 October 2020