Obesity/Type II diabetes alters macrophage polarization resulting in a fibrotic tendon healing response.

Type II Diabetes (T2DM) dramatically impairs the tendon healing response, resulting in decreased collagen organization and mechanics relative to non-diabetic tendons. Despite this burden, there remains a paucity of information regarding the mechanisms that govern impaired healing of diabetic tendons...

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Main Authors: Jessica E Ackerman, Michael B Geary, Caitlin A Orner, Fatima Bawany, Alayna E Loiselle
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5501654?pdf=render
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author Jessica E Ackerman
Michael B Geary
Caitlin A Orner
Fatima Bawany
Alayna E Loiselle
author_facet Jessica E Ackerman
Michael B Geary
Caitlin A Orner
Fatima Bawany
Alayna E Loiselle
author_sort Jessica E Ackerman
collection DOAJ
description Type II Diabetes (T2DM) dramatically impairs the tendon healing response, resulting in decreased collagen organization and mechanics relative to non-diabetic tendons. Despite this burden, there remains a paucity of information regarding the mechanisms that govern impaired healing of diabetic tendons. Mice were placed on either a high fat diet (T2DM) or low fat diet (lean) and underwent flexor tendon transection and repair surgery. Healing was assessed via mechanical testing, histology and changes in gene expression associated with collagen synthesis, matrix remodeling, and macrophage polarization. Obese/diabetic tendons healed with increased scar formation and impaired mechanical properties. Consistent with this, prolonged and excess expression of extracellular matrix (ECM) components were observed in obese/T2DM tendons. Macrophages are involved in both inflammatory and matrix deposition processes during healing. Obese/T2DM tendons healed with increased expression of markers of pro-inflammatory M1 macrophages, and elevated and prolonged expression of M2 macrophages markers that are involved in ECM deposition. Here we demonstrate that tendons from obese/diabetic mice heal with increased scar formation and increased M2 polarization, identifying excess M2 macrophage activity and matrix synthesis as a potential mechanism of the fibrotic healing phenotype observed in T2DM tendons, and as such a potential target to improve tendon healing in T2DM.
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spelling doaj.art-a9dd29b0fef44bdc9003a573d8a9d3332022-12-22T00:49:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01127e018112710.1371/journal.pone.0181127Obesity/Type II diabetes alters macrophage polarization resulting in a fibrotic tendon healing response.Jessica E AckermanMichael B GearyCaitlin A OrnerFatima BawanyAlayna E LoiselleType II Diabetes (T2DM) dramatically impairs the tendon healing response, resulting in decreased collagen organization and mechanics relative to non-diabetic tendons. Despite this burden, there remains a paucity of information regarding the mechanisms that govern impaired healing of diabetic tendons. Mice were placed on either a high fat diet (T2DM) or low fat diet (lean) and underwent flexor tendon transection and repair surgery. Healing was assessed via mechanical testing, histology and changes in gene expression associated with collagen synthesis, matrix remodeling, and macrophage polarization. Obese/diabetic tendons healed with increased scar formation and impaired mechanical properties. Consistent with this, prolonged and excess expression of extracellular matrix (ECM) components were observed in obese/T2DM tendons. Macrophages are involved in both inflammatory and matrix deposition processes during healing. Obese/T2DM tendons healed with increased expression of markers of pro-inflammatory M1 macrophages, and elevated and prolonged expression of M2 macrophages markers that are involved in ECM deposition. Here we demonstrate that tendons from obese/diabetic mice heal with increased scar formation and increased M2 polarization, identifying excess M2 macrophage activity and matrix synthesis as a potential mechanism of the fibrotic healing phenotype observed in T2DM tendons, and as such a potential target to improve tendon healing in T2DM.http://europepmc.org/articles/PMC5501654?pdf=render
spellingShingle Jessica E Ackerman
Michael B Geary
Caitlin A Orner
Fatima Bawany
Alayna E Loiselle
Obesity/Type II diabetes alters macrophage polarization resulting in a fibrotic tendon healing response.
PLoS ONE
title Obesity/Type II diabetes alters macrophage polarization resulting in a fibrotic tendon healing response.
title_full Obesity/Type II diabetes alters macrophage polarization resulting in a fibrotic tendon healing response.
title_fullStr Obesity/Type II diabetes alters macrophage polarization resulting in a fibrotic tendon healing response.
title_full_unstemmed Obesity/Type II diabetes alters macrophage polarization resulting in a fibrotic tendon healing response.
title_short Obesity/Type II diabetes alters macrophage polarization resulting in a fibrotic tendon healing response.
title_sort obesity type ii diabetes alters macrophage polarization resulting in a fibrotic tendon healing response
url http://europepmc.org/articles/PMC5501654?pdf=render
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