Chondroitin sulphate glycosaminoglycans contribute to widespread inferior biomechanics in tendon after focal injury

Choi, Rachel Koeun; Smith, Margaret M.; Martin, Joshua H.; Clark, Julian; Dart, Andrew; Little, Christopher B.; Clarke, Elizabeth C.

doi:10.1016/j.jbiomech.2016.06.006

Cited by 27 publications

(30 citation statements)

References 47 publications

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“…Data are from a single participant as depicted in Figure 1 for (a) and (b) and the healthy control matched participant (c). Abbreviations: A, anterior; L, lateral; M, medial; and P, posterior increase in tendon CSA and AP diameter) throughout the length of tendon is in support of animal models demonstrating that localized tendon injury affects the entire tendon histology, gene expression, composition, and mechanical and morphological properties (Choi et al, 2016). A thicker tendon reduces the average tendon stress (i.e.…”

Section: Tendon Morphology At Restsupporting

confidence: 53%

“…The widespread alteration in tendon morphology of the tendinopathic tendon (i.e. increase in tendon CSA and AP diameter) throughout the length of tendon is in support of animal models demonstrating that localized tendon injury affects the entire tendon histology, gene expression, composition, and mechanical and morphological properties (Choi et al., ). A thicker tendon reduces the average tendon stress (i.e.…”

Section: Discussionmentioning

confidence: 75%

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Three‐dimensional morphology and volume of the free Achilles tendon at rest and under load in people with unilateral mid‐portion Achilles tendinopathy

Nuri

Obst

Newsham-West

et al. 2018

Experimental Physiology

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Mid-portion Achilles tendinopathy (MAT) adversely affects free Achilles tendon (AT) structure and composition. However, it is not known how these pathological alterations associated with MAT change the normal three-dimensional (3-D) morphology of free AT at rest and under load throughout the entire free tendon length. Here, we used 3-D ultrasound to examine the effect of unilateral MAT on free tendon 3-D morphology [length, cross-sectional area (CSA), anteroposterior (AP) diameter and mediolateral (ML) diameter] and volume at rest and during a submaximal (50%) voluntary isometric plantarflexion contraction bilaterally in individuals with unilateral MAT (n = 10) compared with a matched healthy control group (n = 10). The tendinopathic free AT had a greater CSA relative to the control tendons along the entire tendon length, which was mainly driven by a greater tendon AP diameter. Under load, the tendinopathic tendon experienced greater longitudinal and transverse strains than the control tendons. In contrast to the control tendons, which experienced a reduction in tendon CSA and ML diameter, bulged along the AP axis and behaved isovolumetrically under load, the tendinopathic tendon experienced a reduction in tendon CSA, AP diameter and ML diameter and an overall volume reduction. Overall, these findings suggest that the magnitude of longitudinal strain and volume change and the corresponding magnitude and direction of transverse strain under load are altered in MAT compared with normal tendon. These findings are indicative of a fundamental reorganization of the tendon matrix and alterations in tendon fluid content and distribution under load in tendinopathic tendon.

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Section: Tendon Morphology At Restsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 75%

Three‐dimensional morphology and volume of the free Achilles tendon at rest and under load in people with unilateral mid‐portion Achilles tendinopathy

Nuri

Obst

Newsham-West

et al. 2018

Experimental Physiology

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“…Firstly, we assumed that the Achilles tendon material properties were homogeneous, which does not reflect the possibility that tendon material properties could be anisotropic (Bogaerts et al, 2016) and thereby influence the local stress-strains, particularly in the region of the lesion (Chatzistergos et al, 2016). However as the spatial variations of Achilles tendon material properties are as yet unknown, and may even be homogenous in tendinopathy (Choi et al, 2016), this assumption seemed justified in the first instance. Secondly, although we were able to match global strains from our model to experimental data, validation of local strain estimates remains challenging (Maganaris et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Influence of altered geometry and material properties on tissue stress distribution under load in tendinopathic Achilles tendons – A subject-specific finite element analysis

Shim

Hansen

Newsham-West

et al. 2019

Journal of Biomechanics

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Achilles tendon material properties and geometry are altered in Achilles tendinopathy. The purpose of this study was to determine the relative contributions of altered material properties and geometry to free Achilles tendon stress distribution during a sub-maximal contraction in tendinopathic relative to healthy tendons. Tendinopathic (n=8) and healthy tendons (n=8) were imaged at rest and during a sub-maximal voluntary isometric contraction using threedimensional freehand ultrasound. Images were manually segmented and used to create subject-specific finite element models. The resting cross-sectional area of the free tendon was on average 31% greater for the tendinopathic compared to healthy tendons. Material properties for each tendon were determined using a numerical parameter optimisation approach that minimised the difference in experimentally measured longitudinal strain and the strain predicted by the finite element model under submaximal loading conditions for each tendon. The mean Young's modulus for tendinopathic tendons was 53% lower than the corresponding control value. Finite element analyses revealed that tendinopathic tendons experience 24% less stress under the same submaximal external loading conditions compared to healthy tendons. The lower tendon stress in tendinopathy was due to a greater influence of tendon cross-sectional area, which alone reduced tendon stress by 30%, compared to a lower Young's modulus, which alone increased tendon stress by 8%. These findings suggest that the greater tendon cross-sectional area observed in tendinopathy compensates for the substantially lower Young's modulus, thereby protecting pathological tendon against excessive stress.Achilles tendinopathy is a common tendon injury which is prevalent in, but not exclusive to, athletic populations (Kongsgaard et al., 2005;Rolf and Movin, 1997). Up to 25% of affected patients will eventually require operative treatment and 20% of those undergo further surgery (Alfredson, 2003). Achilles tendinopathy is most commonly located in the mid-portion of the free tendon, 2-6 cm from the calcaneal insertion (Astrom and Rausing, 1995;Maffulli et al., 2004;Rolf and Movin, 1997) and is characterised by collagen bundle disruption, hyper-cellularity, hyper-vascularity and altered collagen, glycosaminoglycan and fluid content (Khan et al., 1999). Tendinopathy has also been reported to cause a reduction in tendon mechanical and material properties (Arya and Kulig, 2010;Helland et al., 2013). For the Achilles tendon, stiffness was reduced by 20% and Young's modulus by 50% relative to healthy tendons (Arya and Kulig, 2010). For a tendon of a given length, a lower stiffness would result in greater tendon strain under the same external load. A further adaptation in Achilles tendinopathy is tendon thickening, which increases the tendon cross-sectional area (CSA) by 20-66% (Arya and Kulig, 2010;Helland et al., 2013;Leung and Griffith, 2008;Nuri et al., 2017bNuri et al., , 2018Obst et al., 2018). Tendon thickening may therefore be an adaptation...

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“…Common findings include increased expression of proteoglycans, variable changes in expression of fibrillar collagens, and disturbances in expression of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) at the site of the lesion [25–30]. Recent studies at early post-injury time-points suggest that changes in tendon structure are not localized solely to the area of injury, but distributed up and down the tendon [22, 31]. These widespread changes have been suggested to contribute to a risk of re-injury at a site away from the initial lesion [22], previously observed in equine studies [23].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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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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Chondroitin sulphate glycosaminoglycans contribute to widespread inferior biomechanics in tendon after focal injury

Cited by 27 publications

References 47 publications

Three‐dimensional morphology and volume of the free Achilles tendon at rest and under load in people with unilateral mid‐portion Achilles tendinopathy

Three‐dimensional morphology and volume of the free Achilles tendon at rest and under load in people with unilateral mid‐portion Achilles tendinopathy

Influence of altered geometry and material properties on tissue stress distribution under load in tendinopathic Achilles tendons – A subject-specific finite element analysis

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

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