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IL-1β increases asporin expression via the NF-κB p65 pathway in nucleus pulposus cells during intervertebral disc degeneration
Disc degeneration (DD) is a multifaceted chronic process that alters the structure and function of intervertebral discs. The pathophysiology of degeneration is not completely understood, but the consensus is that changes in genes encoding extracellular matrix (ECM) proteins in the disc are the leadi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482889/ https://www.ncbi.nlm.nih.gov/pubmed/28646230 http://dx.doi.org/10.1038/s41598-017-04384-3 |
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author | Wang, Shengjie Liu, Chao Sun, Zhongyi Yan, Peng Liang, He Huang, Kai Li, Changwei Tian, Jiwei |
author_facet | Wang, Shengjie Liu, Chao Sun, Zhongyi Yan, Peng Liang, He Huang, Kai Li, Changwei Tian, Jiwei |
author_sort | Wang, Shengjie |
collection | PubMed |
description | Disc degeneration (DD) is a multifaceted chronic process that alters the structure and function of intervertebral discs. The pathophysiology of degeneration is not completely understood, but the consensus is that changes in genes encoding extracellular matrix (ECM) proteins in the disc are the leading factors contributing to DD. Asporin is an ECM protein that has been shown to be increased in degenerated intervertebral discs, but little is known about how asporin is regulated during DD. In exploring the intricate mechanism, we confirmed that asporin was abundantly increased in patients’ degenerated nucleus pulposus. Consistently, the increased asporin expression with degeneration was also proved by rabbit intervertebral disc degeneration (IDD) model. Mechanistically, IL-1β upregulated asporin expression by activating the p65 pathway in human nucleus pulposus cells. Furthermore, p65 mediated asporin expression by binding to −41/−31 bp on asporin promoter. Functionally, asporin was the intermediator of IL-1β-inhibited aggrecan and collagen Π expression and played a negative role in TGF-β-induced aggrecan and collagen Π formation in human nucleus pulposus cells. Therefore, identifying asporin as a negative regulator of aggrecan and collagen Π and elucidating its induction mechanisms in human nucleus pulposus cells provides new insight for asporin induction during IDD. |
format | Online Article Text |
id | pubmed-5482889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-54828892017-06-26 IL-1β increases asporin expression via the NF-κB p65 pathway in nucleus pulposus cells during intervertebral disc degeneration Wang, Shengjie Liu, Chao Sun, Zhongyi Yan, Peng Liang, He Huang, Kai Li, Changwei Tian, Jiwei Sci Rep Article Disc degeneration (DD) is a multifaceted chronic process that alters the structure and function of intervertebral discs. The pathophysiology of degeneration is not completely understood, but the consensus is that changes in genes encoding extracellular matrix (ECM) proteins in the disc are the leading factors contributing to DD. Asporin is an ECM protein that has been shown to be increased in degenerated intervertebral discs, but little is known about how asporin is regulated during DD. In exploring the intricate mechanism, we confirmed that asporin was abundantly increased in patients’ degenerated nucleus pulposus. Consistently, the increased asporin expression with degeneration was also proved by rabbit intervertebral disc degeneration (IDD) model. Mechanistically, IL-1β upregulated asporin expression by activating the p65 pathway in human nucleus pulposus cells. Furthermore, p65 mediated asporin expression by binding to −41/−31 bp on asporin promoter. Functionally, asporin was the intermediator of IL-1β-inhibited aggrecan and collagen Π expression and played a negative role in TGF-β-induced aggrecan and collagen Π formation in human nucleus pulposus cells. Therefore, identifying asporin as a negative regulator of aggrecan and collagen Π and elucidating its induction mechanisms in human nucleus pulposus cells provides new insight for asporin induction during IDD. Nature Publishing Group UK 2017-06-23 /pmc/articles/PMC5482889/ /pubmed/28646230 http://dx.doi.org/10.1038/s41598-017-04384-3 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wang, Shengjie Liu, Chao Sun, Zhongyi Yan, Peng Liang, He Huang, Kai Li, Changwei Tian, Jiwei IL-1β increases asporin expression via the NF-κB p65 pathway in nucleus pulposus cells during intervertebral disc degeneration |
title | IL-1β increases asporin expression via the NF-κB p65 pathway in nucleus pulposus cells during intervertebral disc degeneration |
title_full | IL-1β increases asporin expression via the NF-κB p65 pathway in nucleus pulposus cells during intervertebral disc degeneration |
title_fullStr | IL-1β increases asporin expression via the NF-κB p65 pathway in nucleus pulposus cells during intervertebral disc degeneration |
title_full_unstemmed | IL-1β increases asporin expression via the NF-κB p65 pathway in nucleus pulposus cells during intervertebral disc degeneration |
title_short | IL-1β increases asporin expression via the NF-κB p65 pathway in nucleus pulposus cells during intervertebral disc degeneration |
title_sort | il-1β increases asporin expression via the nf-κb p65 pathway in nucleus pulposus cells during intervertebral disc degeneration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482889/ https://www.ncbi.nlm.nih.gov/pubmed/28646230 http://dx.doi.org/10.1038/s41598-017-04384-3 |
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