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Optogenetic-induced muscle loading leads to mechanical adaptation of the Achilles tendon enthesis in mice

Skeletal shape depends on the transmission of contractile muscle forces from tendon to bone across the enthesis. Loss of muscle loading impairs enthesis development, yet little is known if and how the postnatal enthesis adapts to increased loading. Here, we studied adaptations in enthesis structure...

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Autores principales: Ganji, Elahe, Lamia, Syeda N., Stepanovich, Matthew, Whyte, Noelle, Goulet, Robert W., Abraham, Adam C., Killian, Megan L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10289645/
https://www.ncbi.nlm.nih.gov/pubmed/37352350
http://dx.doi.org/10.1126/sciadv.adf4683
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author Ganji, Elahe
Lamia, Syeda N.
Stepanovich, Matthew
Whyte, Noelle
Goulet, Robert W.
Abraham, Adam C.
Killian, Megan L.
author_facet Ganji, Elahe
Lamia, Syeda N.
Stepanovich, Matthew
Whyte, Noelle
Goulet, Robert W.
Abraham, Adam C.
Killian, Megan L.
author_sort Ganji, Elahe
collection PubMed
description Skeletal shape depends on the transmission of contractile muscle forces from tendon to bone across the enthesis. Loss of muscle loading impairs enthesis development, yet little is known if and how the postnatal enthesis adapts to increased loading. Here, we studied adaptations in enthesis structure and function in response to increased loading, using optogenetically induced muscle contraction in young (i.e., growth) and adult (i.e., mature) mice. Daily bouts of unilateral optogenetic loading in young mice led to radial calcaneal expansion and warping. This also led to a weaker enthesis with increased collagen damage in young tendon and enthisis, with little change in adult mice. We then used RNA sequencing to identify the pathways associated with increased mechanical loading during growth. In tendon, we found enrichment of glycolysis, focal adhesion, and cell-matrix interactions. In bone, we found enrichment of inflammation and cell cycle. Together, we demonstrate the utility of optogenetic-induced muscle contraction to elicit in vivo adaptation of the enthesis.
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spelling pubmed-102896452023-06-24 Optogenetic-induced muscle loading leads to mechanical adaptation of the Achilles tendon enthesis in mice Ganji, Elahe Lamia, Syeda N. Stepanovich, Matthew Whyte, Noelle Goulet, Robert W. Abraham, Adam C. Killian, Megan L. Sci Adv Biomedicine and Life Sciences Skeletal shape depends on the transmission of contractile muscle forces from tendon to bone across the enthesis. Loss of muscle loading impairs enthesis development, yet little is known if and how the postnatal enthesis adapts to increased loading. Here, we studied adaptations in enthesis structure and function in response to increased loading, using optogenetically induced muscle contraction in young (i.e., growth) and adult (i.e., mature) mice. Daily bouts of unilateral optogenetic loading in young mice led to radial calcaneal expansion and warping. This also led to a weaker enthesis with increased collagen damage in young tendon and enthisis, with little change in adult mice. We then used RNA sequencing to identify the pathways associated with increased mechanical loading during growth. In tendon, we found enrichment of glycolysis, focal adhesion, and cell-matrix interactions. In bone, we found enrichment of inflammation and cell cycle. Together, we demonstrate the utility of optogenetic-induced muscle contraction to elicit in vivo adaptation of the enthesis. American Association for the Advancement of Science 2023-06-23 /pmc/articles/PMC10289645/ /pubmed/37352350 http://dx.doi.org/10.1126/sciadv.adf4683 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Ganji, Elahe
Lamia, Syeda N.
Stepanovich, Matthew
Whyte, Noelle
Goulet, Robert W.
Abraham, Adam C.
Killian, Megan L.
Optogenetic-induced muscle loading leads to mechanical adaptation of the Achilles tendon enthesis in mice
title Optogenetic-induced muscle loading leads to mechanical adaptation of the Achilles tendon enthesis in mice
title_full Optogenetic-induced muscle loading leads to mechanical adaptation of the Achilles tendon enthesis in mice
title_fullStr Optogenetic-induced muscle loading leads to mechanical adaptation of the Achilles tendon enthesis in mice
title_full_unstemmed Optogenetic-induced muscle loading leads to mechanical adaptation of the Achilles tendon enthesis in mice
title_short Optogenetic-induced muscle loading leads to mechanical adaptation of the Achilles tendon enthesis in mice
title_sort optogenetic-induced muscle loading leads to mechanical adaptation of the achilles tendon enthesis in mice
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10289645/
https://www.ncbi.nlm.nih.gov/pubmed/37352350
http://dx.doi.org/10.1126/sciadv.adf4683
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