EGR2, IGF1 and IL6 Expression Are Elevated in the Intervertebral Disc of Patients Suffering from Diffuse Idiopathic Skeletal Hyperostosis (DISH) Compared to Degenerative or Trauma Discs

Diffuse idiopathic skeletal hyperostosis (DISH) is characterised by ectopic ossification along the anterior spine and the outer intervertebral discs (IVD). However, the centre of the IVD, i.e., the nucleus pulposus, always remains unaffected, which could be due to the inhibition of the bone morphoge...

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Main Authors: Benjamin Gantenbein, Rahel D. May, Paola Bermudez-Lekerika, Katharina A. C. Oswald, Lorin M. Benneker, Christoph E. Albers
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:Applied Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3417/11/9/4072
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author Benjamin Gantenbein
Rahel D. May
Paola Bermudez-Lekerika
Katharina A. C. Oswald
Lorin M. Benneker
Christoph E. Albers
author_facet Benjamin Gantenbein
Rahel D. May
Paola Bermudez-Lekerika
Katharina A. C. Oswald
Lorin M. Benneker
Christoph E. Albers
author_sort Benjamin Gantenbein
collection DOAJ
description Diffuse idiopathic skeletal hyperostosis (DISH) is characterised by ectopic ossification along the anterior spine and the outer intervertebral discs (IVD). However, the centre of the IVD, i.e., the nucleus pulposus, always remains unaffected, which could be due to the inhibition of the bone morphogenetic protein (BMP) pathway. In this study, we investigated the transcriptome for the BMP pathway of DISH-IVD cells versus disc cells of traumatic or degenerative discs. The disc cells originated from nucleus pulposus (NP), annulus fibrosus (AF) and from cartilaginous endplate (CEP) tissue. Here, ninety genes of the transforming growth factor β-BMP signalling pathway were screened by qPCR. Furthermore, the protein expression of genes of interest was further investigated by immune-staining and semi-quantitative microscopy. IVDs of three DISH patients were tested against three control patients (same disc level and similar age). Early Growth Response 2 (<i>EGR2</i>) and Interleukin 6 (<i>IL6</i>) were both significantly up-regulated in DISH-IVD cells compared to controls (12.8 ± 7.6-fold and 54.0 ± 46.5-fold, respectively, means ± SEM). Furthermore, Insulin-like Growth Factor 1 (IGF1) tended to be up-regulated in DISH-IVD donors, i.e., 174.13 ± 120.6-fold. IGF1 was already known as a serum marker for DISH and other rheumatoid diseases and is confirmed here to play a possible key role in DISH-IVD.
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spelling doaj.art-1b4a12e6f7d649208276b6cc805e65752023-11-21T17:48:19ZengMDPI AGApplied Sciences2076-34172021-04-01119407210.3390/app11094072EGR2, IGF1 and IL6 Expression Are Elevated in the Intervertebral Disc of Patients Suffering from Diffuse Idiopathic Skeletal Hyperostosis (DISH) Compared to Degenerative or Trauma DiscsBenjamin Gantenbein0Rahel D. May1Paola Bermudez-Lekerika2Katharina A. C. Oswald3Lorin M. Benneker4Christoph E. Albers5Tissue Engineering for Orthopaedics and Mechanobiology, Department for BioMedical Research (DBMR), University of Bern, CH-3008 Bern, SwitzerlandTissue Engineering for Orthopaedics and Mechanobiology, Department for BioMedical Research (DBMR), University of Bern, CH-3008 Bern, SwitzerlandTissue Engineering for Orthopaedics and Mechanobiology, Department for BioMedical Research (DBMR), University of Bern, CH-3008 Bern, SwitzerlandDepartment of Orthopaedic Surgery and Traumatology, Inselspital, University of Bern, CH-3010 Bern, SwitzerlandDepartment of Orthopaedic Surgery and Traumatology, Inselspital, University of Bern, CH-3010 Bern, SwitzerlandDepartment of Orthopaedic Surgery and Traumatology, Inselspital, University of Bern, CH-3010 Bern, SwitzerlandDiffuse idiopathic skeletal hyperostosis (DISH) is characterised by ectopic ossification along the anterior spine and the outer intervertebral discs (IVD). However, the centre of the IVD, i.e., the nucleus pulposus, always remains unaffected, which could be due to the inhibition of the bone morphogenetic protein (BMP) pathway. In this study, we investigated the transcriptome for the BMP pathway of DISH-IVD cells versus disc cells of traumatic or degenerative discs. The disc cells originated from nucleus pulposus (NP), annulus fibrosus (AF) and from cartilaginous endplate (CEP) tissue. Here, ninety genes of the transforming growth factor β-BMP signalling pathway were screened by qPCR. Furthermore, the protein expression of genes of interest was further investigated by immune-staining and semi-quantitative microscopy. IVDs of three DISH patients were tested against three control patients (same disc level and similar age). Early Growth Response 2 (<i>EGR2</i>) and Interleukin 6 (<i>IL6</i>) were both significantly up-regulated in DISH-IVD cells compared to controls (12.8 ± 7.6-fold and 54.0 ± 46.5-fold, respectively, means ± SEM). Furthermore, Insulin-like Growth Factor 1 (IGF1) tended to be up-regulated in DISH-IVD donors, i.e., 174.13 ± 120.6-fold. IGF1 was already known as a serum marker for DISH and other rheumatoid diseases and is confirmed here to play a possible key role in DISH-IVD.https://www.mdpi.com/2076-3417/11/9/4072low back paindiffuse idiopathic skeletal hyperostosisRNA extractionqPCRTGFβ-pathwayimmune-histochemistry
spellingShingle Benjamin Gantenbein
Rahel D. May
Paola Bermudez-Lekerika
Katharina A. C. Oswald
Lorin M. Benneker
Christoph E. Albers
EGR2, IGF1 and IL6 Expression Are Elevated in the Intervertebral Disc of Patients Suffering from Diffuse Idiopathic Skeletal Hyperostosis (DISH) Compared to Degenerative or Trauma Discs
Applied Sciences
low back pain
diffuse idiopathic skeletal hyperostosis
RNA extraction
qPCR
TGFβ-pathway
immune-histochemistry
title EGR2, IGF1 and IL6 Expression Are Elevated in the Intervertebral Disc of Patients Suffering from Diffuse Idiopathic Skeletal Hyperostosis (DISH) Compared to Degenerative or Trauma Discs
title_full EGR2, IGF1 and IL6 Expression Are Elevated in the Intervertebral Disc of Patients Suffering from Diffuse Idiopathic Skeletal Hyperostosis (DISH) Compared to Degenerative or Trauma Discs
title_fullStr EGR2, IGF1 and IL6 Expression Are Elevated in the Intervertebral Disc of Patients Suffering from Diffuse Idiopathic Skeletal Hyperostosis (DISH) Compared to Degenerative or Trauma Discs
title_full_unstemmed EGR2, IGF1 and IL6 Expression Are Elevated in the Intervertebral Disc of Patients Suffering from Diffuse Idiopathic Skeletal Hyperostosis (DISH) Compared to Degenerative or Trauma Discs
title_short EGR2, IGF1 and IL6 Expression Are Elevated in the Intervertebral Disc of Patients Suffering from Diffuse Idiopathic Skeletal Hyperostosis (DISH) Compared to Degenerative or Trauma Discs
title_sort egr2 igf1 and il6 expression are elevated in the intervertebral disc of patients suffering from diffuse idiopathic skeletal hyperostosis dish compared to degenerative or trauma discs
topic low back pain
diffuse idiopathic skeletal hyperostosis
RNA extraction
qPCR
TGFβ-pathway
immune-histochemistry
url https://www.mdpi.com/2076-3417/11/9/4072
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