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Spatiotemporal variations in gene expression, histology and biomechanics in an ovine model of tendinopathy

Flexor tendinopathy is a common problem affecting humans and animals. Tendon healing is poorly understood and the outcomes of conservative and surgical management are often suboptimal. While often considered a localized injury, recent evidence indicates that in the short term, tendinopathic changes...

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Autores principales: Biasutti, Sara, Dart, Andrew, Smith, Margaret, Blaker, Carina, Clarke, Elizabeth, Jeffcott, Leo, Little, Christopher
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5638251/
https://www.ncbi.nlm.nih.gov/pubmed/29023489
http://dx.doi.org/10.1371/journal.pone.0185282
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author Biasutti, Sara
Dart, Andrew
Smith, Margaret
Blaker, Carina
Clarke, Elizabeth
Jeffcott, Leo
Little, Christopher
author_facet Biasutti, Sara
Dart, Andrew
Smith, Margaret
Blaker, Carina
Clarke, Elizabeth
Jeffcott, Leo
Little, Christopher
author_sort Biasutti, Sara
collection PubMed
description Flexor tendinopathy is a common problem affecting humans and animals. Tendon healing is poorly understood and the outcomes of conservative and surgical management are often suboptimal. While often considered a localized injury, recent evidence indicates that in the short term, tendinopathic changes are distributed widely throughout the tendon, remote from the lesion itself. Whether these changes persist throughout healing is unknown. The aim of this study was to document gene expression, histopathological and biomechanical changes that occur throughout the superficial digital flexor tendon (SDFT) up to 16 weeks post-injury, using an ovine surgical model of tendinopathy. Partial tendon transection was associated with decreased gene expression for aggrecan, decorin, fibromodulin, tissue inhibitors of metalloproteinases (TIMPS 1, 2 and 3), collagen I and collagen II. Gene expression for collagen III, lumican and matrix metalloproteinase 13 (MMP13) increased locally around the lesion site. Expression of collagen III and MMP13 decreased with time, but compared to controls, collagen III, MMP13 and lumican expression remained regionally high throughout the study. An increase in TIMP3 was observed over time. Histologically, operated tendons had higher pathology scores than controls, especially around the injured region. A chondroid phenotype was observed with increased cellular rounding and marked proteoglycan accumulation which only partially improved with time. Biomechanically, partial tendon transection resulted in a localized decrease in elastic modulus (in compression) but only at 8 weeks postoperatively. This study improves our understanding of tendon healing, demonstrating an early ‘peak’ in pathology characterized by altered gene expression and notable histopathological changes. Many of these pathological changes become more localized to the region of injury during healing. Collagen III and MMP13 expression levels remained high close to the lesion throughout the study and may reflect the production of tendon tissue with suboptimal biomechanical properties. Further studies evaluating the long-term response of tendon to injury (6–12 months) are warranted to provide additional information on tendon healing and provide further understanding of the mechanisms underlying the pathology observed in this study.
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spelling pubmed-56382512017-10-20 Spatiotemporal variations in gene expression, histology and biomechanics in an ovine model of tendinopathy Biasutti, Sara Dart, Andrew Smith, Margaret Blaker, Carina Clarke, Elizabeth Jeffcott, Leo Little, Christopher PLoS One Research Article Flexor tendinopathy is a common problem affecting humans and animals. Tendon healing is poorly understood and the outcomes of conservative and surgical management are often suboptimal. While often considered a localized injury, recent evidence indicates that in the short term, tendinopathic changes are distributed widely throughout the tendon, remote from the lesion itself. Whether these changes persist throughout healing is unknown. The aim of this study was to document gene expression, histopathological and biomechanical changes that occur throughout the superficial digital flexor tendon (SDFT) up to 16 weeks post-injury, using an ovine surgical model of tendinopathy. Partial tendon transection was associated with decreased gene expression for aggrecan, decorin, fibromodulin, tissue inhibitors of metalloproteinases (TIMPS 1, 2 and 3), collagen I and collagen II. Gene expression for collagen III, lumican and matrix metalloproteinase 13 (MMP13) increased locally around the lesion site. Expression of collagen III and MMP13 decreased with time, but compared to controls, collagen III, MMP13 and lumican expression remained regionally high throughout the study. An increase in TIMP3 was observed over time. Histologically, operated tendons had higher pathology scores than controls, especially around the injured region. A chondroid phenotype was observed with increased cellular rounding and marked proteoglycan accumulation which only partially improved with time. Biomechanically, partial tendon transection resulted in a localized decrease in elastic modulus (in compression) but only at 8 weeks postoperatively. This study improves our understanding of tendon healing, demonstrating an early ‘peak’ in pathology characterized by altered gene expression and notable histopathological changes. Many of these pathological changes become more localized to the region of injury during healing. Collagen III and MMP13 expression levels remained high close to the lesion throughout the study and may reflect the production of tendon tissue with suboptimal biomechanical properties. Further studies evaluating the long-term response of tendon to injury (6–12 months) are warranted to provide additional information on tendon healing and provide further understanding of the mechanisms underlying the pathology observed in this study. Public Library of Science 2017-10-12 /pmc/articles/PMC5638251/ /pubmed/29023489 http://dx.doi.org/10.1371/journal.pone.0185282 Text en © 2017 Biasutti et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Biasutti, Sara
Dart, Andrew
Smith, Margaret
Blaker, Carina
Clarke, Elizabeth
Jeffcott, Leo
Little, Christopher
Spatiotemporal variations in gene expression, histology and biomechanics in an ovine model of tendinopathy
title Spatiotemporal variations in gene expression, histology and biomechanics in an ovine model of tendinopathy
title_full Spatiotemporal variations in gene expression, histology and biomechanics in an ovine model of tendinopathy
title_fullStr Spatiotemporal variations in gene expression, histology and biomechanics in an ovine model of tendinopathy
title_full_unstemmed Spatiotemporal variations in gene expression, histology and biomechanics in an ovine model of tendinopathy
title_short Spatiotemporal variations in gene expression, histology and biomechanics in an ovine model of tendinopathy
title_sort spatiotemporal variations in gene expression, histology and biomechanics in an ovine model of tendinopathy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5638251/
https://www.ncbi.nlm.nih.gov/pubmed/29023489
http://dx.doi.org/10.1371/journal.pone.0185282
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