Unresolved intramuscular inflammation, not diminished skeletal muscle regenerative capacity, is at the root of rheumatoid cachexia: insights from a rat CIA model

Abstract Rheumatoid arthritis targets numerous organs in patients, including the skeletal muscle, resulting in rheumatoid cachexia. In the muscle niche, satellite cells, macrophages, and myofibroblasts may be affected and the factors they release altered. This study aimed to assess these cell types,...

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Autores principales:	Tracey Ollewagen, Yigael S. L. Powrie, Kathryn H. Myburgh, Carine Smith
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	cachexia collagen‐induced arthritis macrophage myofibroblast satellite cell Physiology QP1-981
Acceso en línea:	https://doaj.org/article/76910b2eadfd4988ba0e5ed9c43d073a
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spelling	oai:doaj.org-article:76910b2eadfd4988ba0e5ed9c43d073a2021-11-27T15:48:30ZUnresolved intramuscular inflammation, not diminished skeletal muscle regenerative capacity, is at the root of rheumatoid cachexia: insights from a rat CIA model2051-817X10.14814/phy2.15119https://doaj.org/article/76910b2eadfd4988ba0e5ed9c43d073a2021-11-01T00:00:00Zhttps://doi.org/10.14814/phy2.15119https://doaj.org/toc/2051-817XAbstract Rheumatoid arthritis targets numerous organs in patients, including the skeletal muscle, resulting in rheumatoid cachexia. In the muscle niche, satellite cells, macrophages, and myofibroblasts may be affected and the factors they release altered. This study aimed to assess these cell types, cytokines, and growth factors and their relationships to muscle fiber size and number in a rodent collagen‐induced arthritis (CIA) model, in order to identify new therapeutic targets. Fiber cross‐sectional area (CSA) was 57% lower in CIA than controls (p < 0.0001), thus smaller but more fibers visible per field of view. Immunostaining indicated the increased presence of satellite cells, macrophages, myofibroblasts, and myonuclei per field of view in CIA (p < 0.01), but this finding was not maintained when taking fiber number into consideration. Western blots of gastrocnemius samples indicated that tumor necrosis factor‐α was significantly elevated (p < 0.01) while interleukin‐10 (IL‐10) was decreased (p < 0.05) in CIA. This effect was maintained (and heightened for IL‐10) when expressed per fiber number. Myogenic regulatory factors (MyoD and myogenin), transforming growth factor‐β and inhibitor of differentiation were significantly elevated in CIA muscle and levels correlated significantly with CSA. Several of these factors remained elevated, but bone morphogenetic protein‐7 decreased when considering fiber number per area. In conclusion, CIA‐muscle demonstrated a good regenerative response. Myoblast numbers per fiber were not elevated, suggesting their activity results from the persistent inflammatory signaling which also significantly hampered maintenance of muscle fiber size. A clearer picture of signaling events at cellular level in arthritis muscle may be derived from expressing data per fiber.Tracey OllewagenYigael S. L. PowrieKathryn H. MyburghCarine SmithWileyarticlecachexiacollagen‐induced arthritismacrophagemyofibroblastsatellite cellPhysiologyQP1-981ENPhysiological Reports, Vol 9, Iss 22, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cachexia collagen‐induced arthritis macrophage myofibroblast satellite cell Physiology QP1-981
spellingShingle	cachexia collagen‐induced arthritis macrophage myofibroblast satellite cell Physiology QP1-981 Tracey Ollewagen Yigael S. L. Powrie Kathryn H. Myburgh Carine Smith Unresolved intramuscular inflammation, not diminished skeletal muscle regenerative capacity, is at the root of rheumatoid cachexia: insights from a rat CIA model
description	Abstract Rheumatoid arthritis targets numerous organs in patients, including the skeletal muscle, resulting in rheumatoid cachexia. In the muscle niche, satellite cells, macrophages, and myofibroblasts may be affected and the factors they release altered. This study aimed to assess these cell types, cytokines, and growth factors and their relationships to muscle fiber size and number in a rodent collagen‐induced arthritis (CIA) model, in order to identify new therapeutic targets. Fiber cross‐sectional area (CSA) was 57% lower in CIA than controls (p < 0.0001), thus smaller but more fibers visible per field of view. Immunostaining indicated the increased presence of satellite cells, macrophages, myofibroblasts, and myonuclei per field of view in CIA (p < 0.01), but this finding was not maintained when taking fiber number into consideration. Western blots of gastrocnemius samples indicated that tumor necrosis factor‐α was significantly elevated (p < 0.01) while interleukin‐10 (IL‐10) was decreased (p < 0.05) in CIA. This effect was maintained (and heightened for IL‐10) when expressed per fiber number. Myogenic regulatory factors (MyoD and myogenin), transforming growth factor‐β and inhibitor of differentiation were significantly elevated in CIA muscle and levels correlated significantly with CSA. Several of these factors remained elevated, but bone morphogenetic protein‐7 decreased when considering fiber number per area. In conclusion, CIA‐muscle demonstrated a good regenerative response. Myoblast numbers per fiber were not elevated, suggesting their activity results from the persistent inflammatory signaling which also significantly hampered maintenance of muscle fiber size. A clearer picture of signaling events at cellular level in arthritis muscle may be derived from expressing data per fiber.
format	article
author	Tracey Ollewagen Yigael S. L. Powrie Kathryn H. Myburgh Carine Smith
author_facet	Tracey Ollewagen Yigael S. L. Powrie Kathryn H. Myburgh Carine Smith
author_sort	Tracey Ollewagen
title	Unresolved intramuscular inflammation, not diminished skeletal muscle regenerative capacity, is at the root of rheumatoid cachexia: insights from a rat CIA model
title_short	Unresolved intramuscular inflammation, not diminished skeletal muscle regenerative capacity, is at the root of rheumatoid cachexia: insights from a rat CIA model
title_full	Unresolved intramuscular inflammation, not diminished skeletal muscle regenerative capacity, is at the root of rheumatoid cachexia: insights from a rat CIA model
title_fullStr	Unresolved intramuscular inflammation, not diminished skeletal muscle regenerative capacity, is at the root of rheumatoid cachexia: insights from a rat CIA model
title_full_unstemmed	Unresolved intramuscular inflammation, not diminished skeletal muscle regenerative capacity, is at the root of rheumatoid cachexia: insights from a rat CIA model
title_sort	unresolved intramuscular inflammation, not diminished skeletal muscle regenerative capacity, is at the root of rheumatoid cachexia: insights from a rat cia model
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/76910b2eadfd4988ba0e5ed9c43d073a
work_keys_str_mv	AT traceyollewagen unresolvedintramuscularinflammationnotdiminishedskeletalmuscleregenerativecapacityisattherootofrheumatoidcachexiainsightsfromaratciamodel AT yigaelslpowrie unresolvedintramuscularinflammationnotdiminishedskeletalmuscleregenerativecapacityisattherootofrheumatoidcachexiainsightsfromaratciamodel AT kathrynhmyburgh unresolvedintramuscularinflammationnotdiminishedskeletalmuscleregenerativecapacityisattherootofrheumatoidcachexiainsightsfromaratciamodel AT carinesmith unresolvedintramuscularinflammationnotdiminishedskeletalmuscleregenerativecapacityisattherootofrheumatoidcachexiainsightsfromaratciamodel
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Unresolved intramuscular inflammation, not diminished skeletal muscle regenerative capacity, is at the root of rheumatoid cachexia: insights from a rat CIA model

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