A novel ex vivo protocol that mimics length and excitation changes of human muscles during walking induces force losses in EDL but not in soleus of mdx mice

Although eccentric contraction protocols are widely used to study the pathophysiology and potential treatments for Duchenne muscular dystrophy (DMD), they do not reflect the stresses, strains, strain rates, and excitation profiles that DMD muscles experience during human daily functional tasks, like...

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Autores: Hu, Xiao, McCrady, Allison N., Bukovec, Katherine E., Yuan, Claire, Miller, Emily Y., Bour, Rachel K., Bruce, Anthony C., Crump, Katherine B., Peirce, Shayn M., Grange, Robert W., Blemker, Silvia S.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:dnet:rdupf_______::e408bf582ba72ce3150b439057845376
Acceso en línea:https://hdl.handle.net/10230/73240
http://dx.doi.org/10.1371/journal.pone.0320901
Access Level:acceso abierto
Palabra clave:Músculs -- Contracció
Caminades
Aparell locomotor
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spelling A novel ex vivo protocol that mimics length and excitation changes of human muscles during walking induces force losses in EDL but not in soleus of mdx miceHu, XiaoMcCrady, Allison N.Bukovec, Katherine E.Yuan, ClaireMiller, Emily Y.Bour, Rachel K.Bruce, Anthony C.Crump, Katherine B.Peirce, Shayn M.Grange, Robert W.Blemker, Silvia S.Músculs -- ContraccióCaminadesAparell locomotorAlthough eccentric contraction protocols are widely used to study the pathophysiology and potential treatments for Duchenne muscular dystrophy (DMD), they do not reflect the stresses, strains, strain rates, and excitation profiles that DMD muscles experience during human daily functional tasks, like walking. This limitation of eccentric contractions may impede our understanding of disease progression in DMD and proper assessment of treatment efficacy. The goals of this study were to examine the extent of force loss induced by a gait cycling protocol we developed, and compare to that from a typical eccentric contraction protocol in soleus and extensor digitorum longus (EDL) muscles of mdx mice. To achieve this goal, mdx soleus and EDL muscles were subjected to eccentric contractions at three levels of strain (10%, 20% and 30% optimal length L) and up to 200 cycles of our gait cycling protocol that mimicked the length changes and excitation patterns of the corresponding muscles during human walking gait. Our results showed that EDL but not soleus muscles had significant losses in isometric tetanic forces after the cycling protocols. Compared to the eccentric contraction protocol, the decrements in contractile performance from the cycling protocol were similar to those from the eccentric contractions at 10% in soleus and 20% L in EDL. Together, these results indicated the gait cycling protocol is a valuable experimental approach to better understand disease progression and to screen and evaluate efficacy of novel therapeutics for DMD.Public Library of Science (PLoS)2026202620252026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/10230/73240http://dx.doi.org/10.1371/journal.pone.0320901reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésPLoS One. 2025 Apr;20(4):e0320901© 2025 Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:dnet:rdupf_______::e408bf582ba72ce3150b4390578453762026-06-12T07:21:37Z
dc.title.none.fl_str_mv A novel ex vivo protocol that mimics length and excitation changes of human muscles during walking induces force losses in EDL but not in soleus of mdx mice
title A novel ex vivo protocol that mimics length and excitation changes of human muscles during walking induces force losses in EDL but not in soleus of mdx mice
spellingShingle A novel ex vivo protocol that mimics length and excitation changes of human muscles during walking induces force losses in EDL but not in soleus of mdx mice
Hu, Xiao
Músculs -- Contracció
Caminades
Aparell locomotor
title_short A novel ex vivo protocol that mimics length and excitation changes of human muscles during walking induces force losses in EDL but not in soleus of mdx mice
title_full A novel ex vivo protocol that mimics length and excitation changes of human muscles during walking induces force losses in EDL but not in soleus of mdx mice
title_fullStr A novel ex vivo protocol that mimics length and excitation changes of human muscles during walking induces force losses in EDL but not in soleus of mdx mice
title_full_unstemmed A novel ex vivo protocol that mimics length and excitation changes of human muscles during walking induces force losses in EDL but not in soleus of mdx mice
title_sort A novel ex vivo protocol that mimics length and excitation changes of human muscles during walking induces force losses in EDL but not in soleus of mdx mice
dc.creator.none.fl_str_mv Hu, Xiao
McCrady, Allison N.
Bukovec, Katherine E.
Yuan, Claire
Miller, Emily Y.
Bour, Rachel K.
Bruce, Anthony C.
Crump, Katherine B.
Peirce, Shayn M.
Grange, Robert W.
Blemker, Silvia S.
author Hu, Xiao
author_facet Hu, Xiao
McCrady, Allison N.
Bukovec, Katherine E.
Yuan, Claire
Miller, Emily Y.
Bour, Rachel K.
Bruce, Anthony C.
Crump, Katherine B.
Peirce, Shayn M.
Grange, Robert W.
Blemker, Silvia S.
author_role author
author2 McCrady, Allison N.
Bukovec, Katherine E.
Yuan, Claire
Miller, Emily Y.
Bour, Rachel K.
Bruce, Anthony C.
Crump, Katherine B.
Peirce, Shayn M.
Grange, Robert W.
Blemker, Silvia S.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Músculs -- Contracció
Caminades
Aparell locomotor
topic Músculs -- Contracció
Caminades
Aparell locomotor
description Although eccentric contraction protocols are widely used to study the pathophysiology and potential treatments for Duchenne muscular dystrophy (DMD), they do not reflect the stresses, strains, strain rates, and excitation profiles that DMD muscles experience during human daily functional tasks, like walking. This limitation of eccentric contractions may impede our understanding of disease progression in DMD and proper assessment of treatment efficacy. The goals of this study were to examine the extent of force loss induced by a gait cycling protocol we developed, and compare to that from a typical eccentric contraction protocol in soleus and extensor digitorum longus (EDL) muscles of mdx mice. To achieve this goal, mdx soleus and EDL muscles were subjected to eccentric contractions at three levels of strain (10%, 20% and 30% optimal length L) and up to 200 cycles of our gait cycling protocol that mimicked the length changes and excitation patterns of the corresponding muscles during human walking gait. Our results showed that EDL but not soleus muscles had significant losses in isometric tetanic forces after the cycling protocols. Compared to the eccentric contraction protocol, the decrements in contractile performance from the cycling protocol were similar to those from the eccentric contractions at 10% in soleus and 20% L in EDL. Together, these results indicated the gait cycling protocol is a valuable experimental approach to better understand disease progression and to screen and evaluate efficacy of novel therapeutics for DMD.
publishDate 2025
dc.date.none.fl_str_mv 2025
2026
2026
2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/10230/73240
http://dx.doi.org/10.1371/journal.pone.0320901
url https://hdl.handle.net/10230/73240
http://dx.doi.org/10.1371/journal.pone.0320901
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv PLoS One. 2025 Apr;20(4):e0320901
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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