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Degeneration of Lumbar Intervertebral Discs: Characterization of Anulus Fibrosus Tissue and Cells of Different Degeneration Grades
Intervertebral disc (IVD) herniation and degeneration is a major source of back pain. In order to regenerate a herniated and degenerated disc, closure of the anulus fibrosus (AF) is of crucial importance. For molecular characterization of AF, genome-wide Affymetrix HG-U133plus2.0 microarrays of nati...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139657/ https://www.ncbi.nlm.nih.gov/pubmed/32245213 http://dx.doi.org/10.3390/ijms21062165 |
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author | Stich, Stefan Jagielski, Michal Fleischmann, Anja Meier, Carola Bussmann, Patricia Kohl, Benjamin Schmidt, Julia Krüger, Jan-Philipp Endres, Michaela Cabraja, Mario Reimann, Kolja Laue, Dominik Ertel, Wolfgang Sittinger, Michael |
author_facet | Stich, Stefan Jagielski, Michal Fleischmann, Anja Meier, Carola Bussmann, Patricia Kohl, Benjamin Schmidt, Julia Krüger, Jan-Philipp Endres, Michaela Cabraja, Mario Reimann, Kolja Laue, Dominik Ertel, Wolfgang Sittinger, Michael |
author_sort | Stich, Stefan |
collection | PubMed |
description | Intervertebral disc (IVD) herniation and degeneration is a major source of back pain. In order to regenerate a herniated and degenerated disc, closure of the anulus fibrosus (AF) is of crucial importance. For molecular characterization of AF, genome-wide Affymetrix HG-U133plus2.0 microarrays of native AF and cultured cells were investigated. To evaluate if cells derived from degenerated AF are able to initiate gene expression of a regenerative pattern of extracellular matrix (ECM) molecules, cultivated cells were stimulated with bone morphogenetic protein 2 (BMP2), transforming growth factor β1 (TGFβ1) or tumor necrosis factor-α (TNFα) for 24 h. Comparative microarray analysis of native AF tissues showed 788 genes with a significantly different gene expression with 213 genes more highly expressed in mild and 575 genes in severe degenerated AF tissue. Mild degenerated native AF tissues showed a higher gene expression of common cartilage ECM genes, whereas severe degenerated AF tissues expressed genes known from degenerative processes, including matrix metalloproteinases (MMP) and bone associated genes. During monolayer cultivation, only 164 differentially expressed genes were found. The cells dedifferentiated and altered their gene expression profile. RTD-PCR analyses of BMP2- and TGFβ1-stimulated cells from mild and severe degenerated AF tissue after 24 h showed an increased expression of cartilage associated genes. TNFα stimulation increased MMP1, 3, and 13 expression. Cells derived from mild and severe degenerated tissues could be stimulated to a comparable extent. These results give hope that regeneration of mildly but also strongly degenerated disc tissue is possible. |
format | Online Article Text |
id | pubmed-7139657 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71396572020-04-10 Degeneration of Lumbar Intervertebral Discs: Characterization of Anulus Fibrosus Tissue and Cells of Different Degeneration Grades Stich, Stefan Jagielski, Michal Fleischmann, Anja Meier, Carola Bussmann, Patricia Kohl, Benjamin Schmidt, Julia Krüger, Jan-Philipp Endres, Michaela Cabraja, Mario Reimann, Kolja Laue, Dominik Ertel, Wolfgang Sittinger, Michael Int J Mol Sci Article Intervertebral disc (IVD) herniation and degeneration is a major source of back pain. In order to regenerate a herniated and degenerated disc, closure of the anulus fibrosus (AF) is of crucial importance. For molecular characterization of AF, genome-wide Affymetrix HG-U133plus2.0 microarrays of native AF and cultured cells were investigated. To evaluate if cells derived from degenerated AF are able to initiate gene expression of a regenerative pattern of extracellular matrix (ECM) molecules, cultivated cells were stimulated with bone morphogenetic protein 2 (BMP2), transforming growth factor β1 (TGFβ1) or tumor necrosis factor-α (TNFα) for 24 h. Comparative microarray analysis of native AF tissues showed 788 genes with a significantly different gene expression with 213 genes more highly expressed in mild and 575 genes in severe degenerated AF tissue. Mild degenerated native AF tissues showed a higher gene expression of common cartilage ECM genes, whereas severe degenerated AF tissues expressed genes known from degenerative processes, including matrix metalloproteinases (MMP) and bone associated genes. During monolayer cultivation, only 164 differentially expressed genes were found. The cells dedifferentiated and altered their gene expression profile. RTD-PCR analyses of BMP2- and TGFβ1-stimulated cells from mild and severe degenerated AF tissue after 24 h showed an increased expression of cartilage associated genes. TNFα stimulation increased MMP1, 3, and 13 expression. Cells derived from mild and severe degenerated tissues could be stimulated to a comparable extent. These results give hope that regeneration of mildly but also strongly degenerated disc tissue is possible. MDPI 2020-03-21 /pmc/articles/PMC7139657/ /pubmed/32245213 http://dx.doi.org/10.3390/ijms21062165 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Stich, Stefan Jagielski, Michal Fleischmann, Anja Meier, Carola Bussmann, Patricia Kohl, Benjamin Schmidt, Julia Krüger, Jan-Philipp Endres, Michaela Cabraja, Mario Reimann, Kolja Laue, Dominik Ertel, Wolfgang Sittinger, Michael Degeneration of Lumbar Intervertebral Discs: Characterization of Anulus Fibrosus Tissue and Cells of Different Degeneration Grades |
title | Degeneration of Lumbar Intervertebral Discs: Characterization of Anulus Fibrosus Tissue and Cells of Different Degeneration Grades |
title_full | Degeneration of Lumbar Intervertebral Discs: Characterization of Anulus Fibrosus Tissue and Cells of Different Degeneration Grades |
title_fullStr | Degeneration of Lumbar Intervertebral Discs: Characterization of Anulus Fibrosus Tissue and Cells of Different Degeneration Grades |
title_full_unstemmed | Degeneration of Lumbar Intervertebral Discs: Characterization of Anulus Fibrosus Tissue and Cells of Different Degeneration Grades |
title_short | Degeneration of Lumbar Intervertebral Discs: Characterization of Anulus Fibrosus Tissue and Cells of Different Degeneration Grades |
title_sort | degeneration of lumbar intervertebral discs: characterization of anulus fibrosus tissue and cells of different degeneration grades |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139657/ https://www.ncbi.nlm.nih.gov/pubmed/32245213 http://dx.doi.org/10.3390/ijms21062165 |
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