Cytokines in tendon disease

Morita, Wataru; Dakin, Stephanie G.; Snelling, Sarah; Carr, Andrew

doi:10.1302/2046-3758.612.bjr-2017-0112.r1

Cited by 65 publications

(69 citation statements)

References 73 publications

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“…Cytokines, such as interleukins, TNF-α, and interferon gamma are known to be key players in tendon disorders. They are released by the tendon stroma or immunoregulatory cells in response to mechanical stress or tissue injury, alter the cellular phenotype, and induce changes in matrix production [62]. Our in vitro data demonstrated the absence of endogenous expression of IL-1β and TNF-α in both groups.…”

Section: Discussionmentioning

confidence: 54%

In Vivo and In Vitro Mechanical Loading of Mouse Achilles Tendons and Tenocytes—A Pilot Study

Fleischhacker

Klatte‐Schulz

Minkwitz

et al. 2020

IJMS

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Mechanical force is a key factor for the maintenance, adaptation, and function of tendons. Investigating the impact of mechanical loading in tenocytes and tendons might provide important information on in vivo tendon mechanobiology. Therefore, the study aimed at understanding if an in vitro loading set up of tenocytes leads to similar regulations of cell shape and gene expression, as loading of the Achilles tendon in an in vivo mouse model. In vivo: The left tibiae of mice (n = 12) were subject to axial cyclic compressive loading for 3 weeks, and the Achilles tendons were harvested. The right tibiae served as the internal non-loaded control. In vitro: tenocytes were isolated from mice Achilles tendons and were loaded for 4 h or 5 days (n = 6 per group) based on the in vivo protocol. Histology showed significant differences in the cell shape between in vivo and in vitro loading. On the molecular level, quantitative real-time PCR revealed significant differences in the gene expression of collagen type I and III and of the matrix metalloproteinases (MMP). Tendon-associated markers showed a similar expression profile. This study showed that the gene expression of tendon markers was similar, whereas significant changes in the expression of extracellular matrix (ECM) related genes were detected between in vivo and in vitro loading. This first pilot study is important for understanding to which extent in vitro stimulation set-ups of tenocytes can mimic in vivo characteristics.

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Section: Discussionmentioning

confidence: 54%

In Vivo and In Vitro Mechanical Loading of Mouse Achilles Tendons and Tenocytes—A Pilot Study

Fleischhacker

Klatte‐Schulz

Minkwitz

et al. 2020

IJMS

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“…Besides, there is an increase of the ratio type III/type I collagen (Birch et al, ; Ireland et al, ; Xu and Murrell, ). Previous studies reported also that there is a decrease of collagen type I at protein level (John et al, ; Schulze‐Tanzil et al, ; Morita et al, ), mainly, because TNF‐ α induces the activation of MMPs and a subsequent degradation of collagen type I (Magra and Maffulli, ; Fang et al, ; Tsai et al, ).…”

Section: Discussionmentioning

confidence: 97%

“…Despite TNF‐α group had a high expression of collagen type I, all the treated group exhibited lower expression showing values closer to that found in tenocytes not subjected to inflammation. The cellular response to treatment with TNF‐α in tendon cells showed an increase of collagen type I (Morita et al, ). In tendinopathy cases, it is noted that there is an increase of expression of type I collagen as well as the percentage of denatured collagen.…”

Section: Discussionmentioning

confidence: 99%

Glycine improves the remodeling process of tenocytes in vitro

Vieira

Viola

Carneiro

et al. 2018

Cell Biology International

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Tendinitis changes the biochemical and morphological properties of the tendon, promoting an increase of activity of metalloproteinases and disorganization of collagen bundles. Tenocytes, the primary cells in tendon, are scattered throughout the collagenic fibers, and are responsible of tendon remodeling and tissue repair in pathological condition. In vivo, glycine, component of the typical Gly-X-Y collagen tripeptide, showed beneficial effects in biochemical and biomechanical properties of Achilles tendon with tendinitis. In this study, we analyzed the effect of glycine in tenocytes subjected to inflammation. Tenocytes from Achilles tendon of rats were treated with TNF-α (10 ng/mL) with and without previous treatment with glycine (20 mM). Cell proliferation and migration were evaluated, as well as the expression of matrix molecules such as glycosaminoglycans, metalloproteinases (MMPs), TIMPs, and collagen I. Glycine can revert the inflammation due to the action of TNF-α by controlling the MMPs quantity and activity. These data indicated that the molecules involved to remodeling process of extracellular matrix are modulated both by TNF-α and the availability of collagen precursors; in fact, this study indicates the glycine can be useful for treatment of inflammation and for modulating tenocytes metabolism in tendons.

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“… 40 A systematic review on cytokines in tendon disease showed that the expressions of IL-1β, IL-6 and TNF-α in animal tendon injury models tend to increase from the early phase of tendon healing, whereas IL-6 was the only cytokine involved in human tendon disease and found to be elevated in tendon tears. 41 Further investigation is needed into the role of these cytokines in the development of tendon disease. In this study, the higher expression of IL-6 in tenocytes in vitro and Achilles tendon from diabetic rats was seen under high glucose conditions.…”

Section: Discussionmentioning

confidence: 99%

The effects of high glucose condition on rat tenocytes in vitro and rat Achilles tendon in vivo

Ueda

Inui

Mifune

et al. 2018

Bone & Joint Research

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ObjectivesThe aim of this study was to investigate the effect of hyperglycaemia on oxidative stress markers and inflammatory and matrix gene expression within tendons of normal and diabetic rats and to give insights into the processes involved in tendinopathy.MethodsUsing tenocytes from normal Sprague-Dawley rats, cultured both in control and high glucose conditions, reactive oxygen species (ROS) production, cell proliferation, messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, interleukin-6 (IL-6), matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -2 and type I and III collagens were determined after 48 and 72 hours in vitro. In an in vivo study, using diabetic rats and controls, NOX1 and 4 expressions in Achilles tendon were also determined.ResultsIn tenocyte cultures grown under high glucose conditions, gene expressions of NOX1, MMP-2, TIMP-1 and -2 after 48 and 72 hours, NOX4 after 48 hours and IL-6, type III collagen and TIMP-2 after 72 hours were significantly higher than those in control cultures grown under control glucose conditions. Type I collagen expression was significantly lower after 72 hours. ROS accumulation was significantly higher after 48 hours, and cell proliferation after 48 and 72 hours was significantly lower in high glucose than in control glucose conditions. In the diabetic rat model, NOX1 expression within the Achilles tendon was also significantly increased.ConclusionThis study suggests that high glucose conditions upregulate the expression of mRNA for NOX1 and IL-6 and the production of ROS. Moreover, high glucose conditions induce an abnormal tendon matrix expression pattern of type I collagen and a decrease in the proliferation of rat tenocytes.Cite this article: Y. Ueda, A. Inui, Y. Mifune, R. Sakata, T. Muto, Y. Harada, F. Takase, T. Kataoka, T. Kokubu, R. Kuroda. The effects of high glucose condition on rat tenocytes in vitro and rat Achilles tendon in vivo. Bone Joint Res 2018;7:362–372. DOI: 10.1302/2046-3758.75.BJR-2017-0126.R2

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Cytokines in tendon disease

Cited by 65 publications

References 73 publications

In Vivo and In Vitro Mechanical Loading of Mouse Achilles Tendons and Tenocytes—A Pilot Study

In Vivo and In Vitro Mechanical Loading of Mouse Achilles Tendons and Tenocytes—A Pilot Study

Glycine improves the remodeling process of tenocytes in vitro

The effects of high glucose condition on rat tenocytes in vitro and rat Achilles tendon in vivo

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