Co-transfection of decorin and interleukin-10 modulates pro-fibrotic extracellular matrix gene expression in human tenocyte culture

Abbah, Sunny Akogwu; Thomas, Dilip; Browne, Stephen; O’Brien, Timothy; Pandit, Abhay; Zeugolis, Dimitrios I.

doi:10.1038/srep20922

Cited by 34 publications

(22 citation statements)

References 76 publications

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“…1–4h) and that the 24h levels might be determined by the rate of removal for translation. In addition differences in TGFβ-mediated effects might result from a) modified turnover of TGFβ receptor proteins and/or associated kinase activities, b) altered levels of TGFβ “companion” proteins such as WFIKKN1 [23]) and/or c) over-production of TGFβ1 signaling antagonists such as decorin or IL-10 [24]).…”

Section: Resultsmentioning

confidence: 99%

Degenerative Suspensory Ligament Desmitis (DSLD) in Peruvian Paso Horses Is Characterized by Altered Expression of TGFβ Signaling Components in Adipose-Derived Stromal Fibroblasts

et al. 2016

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Equine degenerative suspensory ligament desmitis (DSLD) in Peruvian Paso horses typically presents at 7–15 years and is characterized by lameness, focal disorganization of collagen fibrils, and chondroid deposition in the body of the ligament. With the aim of developing a test for disease risk (that can be used to screen horses before breeding) we have quantified the expression of 76 TGFβ-signaling target genes in adipose-derived stromal fibroblasts (ADSCs) from six DSLD-affected and five unaffected Paso horses. Remarkably, 35 of the genes showed lower expression (p<0.05) in cells from DSLD-affected animals and this differential was largely eliminated by addition of exogenous TGFβ1. Moreover, TGFβ1-mediated effects on expression were prevented by the TGFβR1/2 inhibitor LY2109761, showing that the signaling was via a TGFβR1/2 complex. The genes affected by the pathology indicate that it is associated with a generalized metabolic disturbance, since some of those most markedly altered in DSLD cells (ATF3, MAPK14, ACVRL1 (ALK1), SMAD6, FOS, CREBBP, NFKBIA, and TGFBR2) represent master-regulators in a wide range of cellular metabolic responses.

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Section: Resultsmentioning

confidence: 99%

Degenerative Suspensory Ligament Desmitis (DSLD) in Peruvian Paso Horses Is Characterized by Altered Expression of TGFβ Signaling Components in Adipose-Derived Stromal Fibroblasts

et al. 2016

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“…Despite these challenges, decellularized tendon tissue allografts have been evaluated in small and large animal models and showed some promise in augmenting tendon repair after injury . In addition, overexpression or exogenous addition of individual ECM proteins in combination with a diverse set of growth factors have been shown to enhance tenogenic differentiation of stem cells and augment repair processes in injury models, respectively, and as such could represent an integral part of a comprehensive tendon tissue engineering and repair strategy . An understanding of the dynamic tendon ECM and tenocyte PCM will provide useful guidance to design future therapeutic approaches to augment tendon healing and to invigorate tendon tissue engineering.…”

Section: Non‐collagenous Ecm Proteins In Tendon Tissue Engineeringmentioning

confidence: 99%

“…173 OTHER ECM PROTEINS IN TENDON combination with a diverse set of growth factors have been shown to enhance tenogenic differentiation of stem cells and augment repair processes in injury models, respectively, and as such could represent an integral part of a comprehensive tendon tissue engineering and repair strategy. 74,[180][181][182] An understanding of the dynamic tendon ECM and tenocyte PCM will provide useful guidance to design future therapeutic approaches to augment tendon healing and to invigorate tendon tissue engineering.…”

Section: Non-collagenous Ecm Proteins In Tendon Tissue Engineeringmentioning

confidence: 99%

The “other” 15–40%: The Role of Non‐Collagenous Extracellular Matrix Proteins and Minor Collagens in Tendon

Taye

Karoulias

Hubmacher

2019

Journal Orthopaedic Research

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Extracellular matrix (ECM) determines the physiological function of all tissues, including musculoskeletal tissues. In tendon, ECM provides overall tissue architecture, which is tailored to match the biomechanical requirements of their physiological function, that is, force transmission from muscle to bone. Tendon ECM also constitutes the microenvironment that allows tendon‐resident cells to maintain their phenotype and that transmits biomechanical forces from the macro‐level to the micro‐level. The structure and function of adult tendons is largely determined by the hierarchical organization of collagen type I fibrils. However, non‐collagenous ECM proteins such as small leucine‐rich proteoglycans (SLRPs), ADAMTS proteases, and cross‐linking enzymes play critical roles in collagen fibrillogenesis and guide the hierarchical bundling of collagen fibrils into tendon fascicles. Other non‐collagenous ECM proteins such as the less abundant collagens, fibrillins, or elastin, contribute to tendon formation or determine some of their biomechanical properties. The interfascicular matrix or endotenon and the outer layer of tendons, the epi‐ and paratenon, includes collagens and non‐collagenous ECM proteins, but their function is less well understood. The ECM proteins in the epi‐ and paratenon may provide the appropriate microenvironment to maintain the identity of distinct tendon cell populations that are thought to play a role during repair processes after injury. The aim of this review is to provide an overview of the role of non‐collagenous ECM proteins and less abundant collagens in tendon development and homeostasis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:23–35, 2020

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“…Clinically, PDGF receptor expression is increased in diseased tendons, and is associated with hypercellularity 32 , and taken into context with our findings on the poor effects of PDGF on tendon-related genes, this suggests that PDGF may not be the most suitable factor for improving tendon healing outcomes. IGF-1 and TGF-β are both present within the tendon matrix 18 , and in vitro have been shown to be involved in tendon cell growth, collagen production and matrix remodelling [19][20][21][22][23][24][25] . Developmental studies suggest a key role for TGFβ1 in tendon development 33 , and inhibiting TGFβ1 has generally resulted in poor healing outcomes in in vivo tendon defect models 34 .…”

Section: Discussionmentioning

confidence: 99%

“…These were chosen as PDGF is among the most widely studied tendon factors, and IGF-1 and TGF-β are both present within the tendon matrix. Furthermore, all are upregulated during tendon healing, and are known to enhance tendon cell growth, collagen production and matrix remodelling, in vitro [18][19][20][21][22][23][24][25][26] . Furthermore, we have focussed on not only classical tendon-related outputs, such as cell proliferation and collagen production, we have also assessed the tenocyte gene expression profile, assessing genes important in tenocyte, chondrocyte and osteoblast biology.…”

Section: Introductionmentioning

confidence: 99%

Lactoferrin and parathyroid hormone are not harmful to primary tenocytes in vitro, but PDGF may be

Musson

Tay

Chhana

et al. 2017

MLTJ

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SummaryIntroduction: Recently, bone-active factors such as parathyroid hormone and lactoferrin, have been used in pre-clinical models to promote tendon healing. How-ever, there is limited understanding of how these boneactive factors may affect the cells of the ten-don themselves. Here, we present an in vitro study assessing the effects of parathyroid hor-mone and lactoferrin on primary tendon cells (tenocytes), and compare their responses to the tenogenic factors, PDGF, IGF-1 and TGF-β. Materials and Methods: Tenocyte proliferation and collagen production were assessed by alamarBlue® and Sirius red as-says, respectively. To assess tenocyte trans-differentiation, changes in the expression of genes important in tenocyte, chondrocyte and osteoblast biology were determined using real-time PCR. Results: Parathyroid hormone and lactoferrin had no effect on tenocyte growth or collagen production, with minimal changes in gene expression and no detrimental effects observed to suggest trans-differentiation away from tendon cell behaviour. Tenogenic factors PDGF, IGF-1 and TGF all increasetenocyte collagen production, however, the gene expression data suggests that PDGF promotes severe de-differentiation of the tenocytes. Discussion: Our findings suggest that using parathyroid hormone or lactoferrin as a singular factor to promote tendon healing may not be of benefit, but for use in tendon-bone healing there would be no detrimental effect on the tendon itself.

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Co-transfection of decorin and interleukin-10 modulates pro-fibrotic extracellular matrix gene expression in human tenocyte culture

Cited by 34 publications

References 76 publications

Degenerative Suspensory Ligament Desmitis (DSLD) in Peruvian Paso Horses Is Characterized by Altered Expression of TGFβ Signaling Components in Adipose-Derived Stromal Fibroblasts

Degenerative Suspensory Ligament Desmitis (DSLD) in Peruvian Paso Horses Is Characterized by Altered Expression of TGFβ Signaling Components in Adipose-Derived Stromal Fibroblasts

The “other” 15–40%: The Role of Non‐Collagenous Extracellular Matrix Proteins and Minor Collagens in Tendon

Lactoferrin and parathyroid hormone are not harmful to primary tenocytes in vitro, but PDGF may be

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