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Inflammatory profiles in canine intervertebral disc degeneration

BACKGROUND: Intervertebral disc (IVD) disease is a common spinal disorder in dogs and degeneration and inflammation are significant components of the pathological cascade. Only limited studies have studied the cytokine and chemokine profiles in IVD degeneration in dogs, and mainly focused on gene ex...

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Autores principales: Willems, Nicole, Tellegen, Anna R., Bergknut, Niklas, Creemers, Laura B., Wolfswinkel, Jeannette, Freudigmann, Christian, Benz, Karin, Grinwis, Guy C. M., Tryfonidou, Marianna A., Meij, Björn P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711078/
https://www.ncbi.nlm.nih.gov/pubmed/26757881
http://dx.doi.org/10.1186/s12917-016-0635-6
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author Willems, Nicole
Tellegen, Anna R.
Bergknut, Niklas
Creemers, Laura B.
Wolfswinkel, Jeannette
Freudigmann, Christian
Benz, Karin
Grinwis, Guy C. M.
Tryfonidou, Marianna A.
Meij, Björn P.
author_facet Willems, Nicole
Tellegen, Anna R.
Bergknut, Niklas
Creemers, Laura B.
Wolfswinkel, Jeannette
Freudigmann, Christian
Benz, Karin
Grinwis, Guy C. M.
Tryfonidou, Marianna A.
Meij, Björn P.
author_sort Willems, Nicole
collection PubMed
description BACKGROUND: Intervertebral disc (IVD) disease is a common spinal disorder in dogs and degeneration and inflammation are significant components of the pathological cascade. Only limited studies have studied the cytokine and chemokine profiles in IVD degeneration in dogs, and mainly focused on gene expression. A better understanding is needed in order to develop biological therapies that address both pain and degeneration in IVD disease. Therefore, in this study, we determined the levels of prostaglandin E2 (PGE(2)), cytokines, chemokines, and matrix components in IVDs from chondrodystrophic (CD) and non-chondrodystrophic (NCD) dogs with and without clinical signs of IVD disease, and correlated these to degeneration grade (according to Pfirrmann), or herniation type (according to Hansen). In addition, we investigated cyclooxygenase 2 (COX-2) expression and signs of inflammation in histological IVD samples of CD and NCD dogs. RESULTS: PGE(2) levels were significantly higher in the nucleus pulposus (NP) of degenerated IVDs compared with non-degenerated IVDs, and in herniated IVDs from NCD dogs compared with non-herniated IVDs of NCD dogs. COX-2 expression in the NP and annulus fibrosus (AF), and proliferation of fibroblasts and numbers of macrophages in the AF significantly increased with increased degeneration grade. GAG content did not significantly change with degeneration grade or herniation type. Cytokines interleukin (IL)-2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, immune protein (IP)-10, tumor necrosis factor (TNF)-α, and granulocyte macrophage colony-stimulating factor (GM-CSF) were not detectable in the samples. Chemokine (C-C) motif ligand (CCL)2 levels in the NP from extruded samples were significantly higher compared with the AF of these samples and the NP from protrusion samples. CONCLUSIONS: PGE(2) levels and CCL2 levels in degenerated and herniated IVDs were significantly higher compared with non-degenerated and non-herniated IVDs. COX-2 expression in the NP and AF and reactive changes in the AF increased with advancing degeneration stages. Although macrophages invaded the AF as degeneration progressed, the production of inflammatory mediators seemed most pronounced in degenerated NP tissue. Future studies are needed to investigate if inhibition of PGE(2) levels in degenerated IVDs provides effective analgesia and exerts a protective role in the process of IVD degeneration and the development of IVD disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-016-0635-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-47110782016-01-14 Inflammatory profiles in canine intervertebral disc degeneration Willems, Nicole Tellegen, Anna R. Bergknut, Niklas Creemers, Laura B. Wolfswinkel, Jeannette Freudigmann, Christian Benz, Karin Grinwis, Guy C. M. Tryfonidou, Marianna A. Meij, Björn P. BMC Vet Res Research Article BACKGROUND: Intervertebral disc (IVD) disease is a common spinal disorder in dogs and degeneration and inflammation are significant components of the pathological cascade. Only limited studies have studied the cytokine and chemokine profiles in IVD degeneration in dogs, and mainly focused on gene expression. A better understanding is needed in order to develop biological therapies that address both pain and degeneration in IVD disease. Therefore, in this study, we determined the levels of prostaglandin E2 (PGE(2)), cytokines, chemokines, and matrix components in IVDs from chondrodystrophic (CD) and non-chondrodystrophic (NCD) dogs with and without clinical signs of IVD disease, and correlated these to degeneration grade (according to Pfirrmann), or herniation type (according to Hansen). In addition, we investigated cyclooxygenase 2 (COX-2) expression and signs of inflammation in histological IVD samples of CD and NCD dogs. RESULTS: PGE(2) levels were significantly higher in the nucleus pulposus (NP) of degenerated IVDs compared with non-degenerated IVDs, and in herniated IVDs from NCD dogs compared with non-herniated IVDs of NCD dogs. COX-2 expression in the NP and annulus fibrosus (AF), and proliferation of fibroblasts and numbers of macrophages in the AF significantly increased with increased degeneration grade. GAG content did not significantly change with degeneration grade or herniation type. Cytokines interleukin (IL)-2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, immune protein (IP)-10, tumor necrosis factor (TNF)-α, and granulocyte macrophage colony-stimulating factor (GM-CSF) were not detectable in the samples. Chemokine (C-C) motif ligand (CCL)2 levels in the NP from extruded samples were significantly higher compared with the AF of these samples and the NP from protrusion samples. CONCLUSIONS: PGE(2) levels and CCL2 levels in degenerated and herniated IVDs were significantly higher compared with non-degenerated and non-herniated IVDs. COX-2 expression in the NP and AF and reactive changes in the AF increased with advancing degeneration stages. Although macrophages invaded the AF as degeneration progressed, the production of inflammatory mediators seemed most pronounced in degenerated NP tissue. Future studies are needed to investigate if inhibition of PGE(2) levels in degenerated IVDs provides effective analgesia and exerts a protective role in the process of IVD degeneration and the development of IVD disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-016-0635-6) contains supplementary material, which is available to authorized users. BioMed Central 2016-01-13 /pmc/articles/PMC4711078/ /pubmed/26757881 http://dx.doi.org/10.1186/s12917-016-0635-6 Text en © Willems et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Willems, Nicole
Tellegen, Anna R.
Bergknut, Niklas
Creemers, Laura B.
Wolfswinkel, Jeannette
Freudigmann, Christian
Benz, Karin
Grinwis, Guy C. M.
Tryfonidou, Marianna A.
Meij, Björn P.
Inflammatory profiles in canine intervertebral disc degeneration
title Inflammatory profiles in canine intervertebral disc degeneration
title_full Inflammatory profiles in canine intervertebral disc degeneration
title_fullStr Inflammatory profiles in canine intervertebral disc degeneration
title_full_unstemmed Inflammatory profiles in canine intervertebral disc degeneration
title_short Inflammatory profiles in canine intervertebral disc degeneration
title_sort inflammatory profiles in canine intervertebral disc degeneration
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711078/
https://www.ncbi.nlm.nih.gov/pubmed/26757881
http://dx.doi.org/10.1186/s12917-016-0635-6
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