Potential roles for the small leucine‐rich proteoglycans biglycan and fibromodulin in ectopic ossification of tendon induced by exercise and in modulating rotarod performance

Kilts, Tina M.; Ameye, Laurent; Syed-Picard, Fatima N.; Ono, M.; Berendsen, Agnes D.; Oldberg, Åke; Heegaard, Anne‐Marie; Bi, Yanming; Young, Marian F.

doi:10.1111/j.1600-0838.2009.00909.x

Cited by 34 publications

(44 citation statements)

References 36 publications

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“…Regional distribution of SLRPs within tendons may play a role. Although regional differences in proteoglycans and GAGs between tendons and within a single tendon have been noted both biochemically and mechanically (Buckley et al, 2013a, 2013b, 2013c; Matuszewski et al, 2012; Merrilees and Flint, 1980; Rigozzi et al, 2009; Thomopoulos et al, 2003; Kilts et al, 2009), significant work is needed to fully characterize the significance of these relationships.…”

Section: Discussionmentioning

confidence: 99%

Achilles tendons from decorin- and biglycan-null mouse models have inferior mechanical and structural properties predicted by an image-based empirical damage model

Gordon¹,

Freedman²,

Zuskov³

et al. 2015

Journal of Biomechanics

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Achilles tendons are a common source of pain and injury, and their pathology may originate from aberrant structure function relationships. Small leucine rich proteoglycans (SLRPs) influence mechanical and structural properties in a tendon-specific manner. However, their roles in the Achilles tendon have not been defined. The objective of this study was to evaluate the mechanical and structural differences observed in mouse Achilles tendons lacking class I SLRPs; either decorin or biglycan. In addition, empirical modeling techniques based on mechanical and image-based measures were employed. Achilles tendons from decorin-null (Dcn−/−) and biglycan-null (Bgn−/−) C57BL/6 female mice (N=102) were used. Each tendon underwent a dynamic mechanical testing protocol including simultaneous polarized light image capture to evaluate both structural and mechanical properties of each Achilles tendon. An empirical damage model was adapted for application to genetic variation and for use with image based structural properties to predict tendon dynamic mechanical properties. We found that Achilles tendons lacking decorin and biglycan had inferior mechanical and structural properties that were age dependent; and that simple empirical models, based on previously described damage models, were predictive of Achilles tendon dynamic modulus in both decorin- and biglycan-null mice.

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Section: Discussionmentioning

confidence: 99%

Achilles tendons from decorin- and biglycan-null mouse models have inferior mechanical and structural properties predicted by an image-based empirical damage model

Gordon¹,

Freedman²,

Zuskov³

et al. 2015

Journal of Biomechanics

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“…Decorin (named because of its ability to decorate collagen fibrils 15 ) is one of the most widely studied class I SLRPs in tendon, alongside biglycan 16; 17 (named because it contains two chains of attached glycosaminoglycans (GAGS)). The class II SLRPs fibromodulin 18 and lumican 13; 19; 20 are also present in tendon and, like decorin and biglycan, appear to have unique, but overlapping functions in fine-tuning collagen fibril assembly and subsequent tendon integrity 19; 20; 21; 22; 23; 24 .…”

Section: Tendon Compositionmentioning

confidence: 99%

Tendon Functional Extracellular Matrix

Screen

Berk²,

Kadler

et al. 2015

Journal Orthopaedic Research

192

157

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This article is one of a series, summarising views expressed at the Orthopaedic Research Society New Frontiers in Tendon Research Conference. This particular article reviews the three workshops held under the “Functional Extracellular Matrix” stream. The workshops focused on the roles of the tendon extracellular matrix, such as performing the mechanical functions of tendon, creating the local cell environment and providing cellular cues. Tendon is a complex network of matrix and cells, and its biological functions are influenced by widely-varying extrinsic and intrinsic factors such as age, nutrition, exercise levels and biomechanics. Consequently, tendon adapts dynamically during development, ageing and injury. The workshop discussions identified research directions associated with understanding cell-matrix interactions to be of prime importance for developing novel strategies to target tendon healing or repair.

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“…Biglycan-null mice ( Bgn −/−) have a known tail tendon fibril phenotype marked by greater irregularity in both size and shape (Corsi et al, 2002). In addition, these mice have diminished bone mass, that becomes increasingly pronounced with age, have been used as a model for osteoporosis (Xu et al, 1998; Young et al, 2002), and suffer ectopic ossification of their tendons (Kilts et al, 2009). A mechanism by which biglycan, with fibromodulin, affects the differentiation of tendon stem/progenitor cells (TSPCs) has been proposed to explain these effects (Bi et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Decorin expression is important for age-related changes in tendon structure and mechanical properties

et al. 2013

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The aging population is at an increased risk of tendon injury and tendinopathy. Elucidating the molecular basis of tendon aging is crucial to understanding the age-related changes in structure and function in this vulnerable tissue. In this study, the structural and functional features of tendon aging are investigated. In addition, the roles of decorin and biglycan in the aging process were analyzed using transgenic mice at both mature and aged time points. Our hypothesis is that the increase in tendon injuries in the aging population is the result of altered structural properties that reduce the biomechanical function of the tendon and consequently increase susceptibility to injury. Decorin and biglycan are important regulators of tendon structure and therefore, we further hypothesized that decreased function in aged tendons is partly the result of altered decorin and biglycan expression. Biomechanical analyses of mature (day 150) and aged (day 570) patellar tendons revealed deteriorating viscoelastic properties with age. Histology and polarized light microscopy demonstrated decreased cellularity, alterations in tenocyte shape, and reduced collagen fiber alignment in the aged tendons. Ultrastructural analysis of fibril diameter distributions indicated an altered distribution in aged tendons with an increase of large diameter fibrils. Aged wild type tendons maintained expression of decorin which was associated with the structural and functional changes seen in aged tendons. Aged patellar tendons exhibited altered and generally inferior properties across multiple assays. However, decorin-null tendons exhibited significantly decreased effects of aging compared to the other genotypes. The amelioration of the functional deficits seen in the absence of decorin in aged tendons was associated with altered tendon fibril structure. Fibril diameter distributions in the decorin-null aged tendons were comparable to those observed in the mature wild type tendon with the absence of the subpopulation containing large diameter fibrils. Collectively, our findings provide evidence for age-dependent alterations in tendon architecture and functional activity, and further show that lack of stromal decorin attenuates these changes.

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Potential roles for the small leucine‐rich proteoglycans biglycan and fibromodulin in ectopic ossification of tendon induced by exercise and in modulating rotarod performance

Cited by 34 publications

References 36 publications

Achilles tendons from decorin- and biglycan-null mouse models have inferior mechanical and structural properties predicted by an image-based empirical damage model

Achilles tendons from decorin- and biglycan-null mouse models have inferior mechanical and structural properties predicted by an image-based empirical damage model

Tendon Functional Extracellular Matrix

Decorin expression is important for age-related changes in tendon structure and mechanical properties

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