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miR‐640 aggravates intervertebral disc degeneration via NF‐κB and WNT signalling pathway
OBJECTIVES: Low back pain becomes a common orthopaedic disease today. It is mainly induced by the degeneration of the intervertebral disc. In this study, we tried to reveal the pathogenesis of the degeneration and the relative therapeutic strategy, which are still elusive. MATERIALS AND METHODS: We...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797513/ https://www.ncbi.nlm.nih.gov/pubmed/31343104 http://dx.doi.org/10.1111/cpr.12664 |
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author | Dong, Wengang Liu, Jun Lv, Yang Wang, Fei Liu, Tao Sun, Siguo Liao, Bo Shu, Zhen Qian, Jixian |
author_facet | Dong, Wengang Liu, Jun Lv, Yang Wang, Fei Liu, Tao Sun, Siguo Liao, Bo Shu, Zhen Qian, Jixian |
author_sort | Dong, Wengang |
collection | PubMed |
description | OBJECTIVES: Low back pain becomes a common orthopaedic disease today. It is mainly induced by the degeneration of the intervertebral disc. In this study, we tried to reveal the pathogenesis of the degeneration and the relative therapeutic strategy, which are still elusive. MATERIALS AND METHODS: We collected 15 degenerative intervertebral tissues and five healthy donors. Nucleus pulposus and annulus fibrosus cells were subcultured. miR‐640 expression was determined by qPCR. Computer analysis and luciferase reporter assay were used to confirm miR‐640 target genes. Immunohistochemical and immunocytochemical staining was used to trace the proinflammatory cytokines and key transductor of signalling pathways. We also used β‐galactosidase staining, flow cytometry, and cell viability assay to monitor the degenerative index. RESULTS: miR‐640 overexpressed in patients derived degenerative nucleus pulposus tissues and cells. The inflammatory environment promoted miR‐640 expression via NF‐κB signalling pathway. In addition, miR‐640 targeted to LRP1 and enhances NF‐κB signal activity, which built a positive feedback loop. miR‐640 inhibited the expression of β‐catenin and EP300, therefore, restrained WNT signal and induced the degeneration in nucleus pulposus cells. miR‐640 inhibitor treatment exhibited the effects of anti‐inflammation, reverse WNT signalling pathway exhaustion, and remission of degenerative characteristics in vitro. CONCLUSIONS: miR‐640 plays an important role in the degeneration of intervertebral disc and the relative inflammatory microenvironment. It is a promising potential therapeutic target for the low back pain biotherapy. |
format | Online Article Text |
id | pubmed-6797513 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67975132020-03-13 miR‐640 aggravates intervertebral disc degeneration via NF‐κB and WNT signalling pathway Dong, Wengang Liu, Jun Lv, Yang Wang, Fei Liu, Tao Sun, Siguo Liao, Bo Shu, Zhen Qian, Jixian Cell Prolif Original Articles OBJECTIVES: Low back pain becomes a common orthopaedic disease today. It is mainly induced by the degeneration of the intervertebral disc. In this study, we tried to reveal the pathogenesis of the degeneration and the relative therapeutic strategy, which are still elusive. MATERIALS AND METHODS: We collected 15 degenerative intervertebral tissues and five healthy donors. Nucleus pulposus and annulus fibrosus cells were subcultured. miR‐640 expression was determined by qPCR. Computer analysis and luciferase reporter assay were used to confirm miR‐640 target genes. Immunohistochemical and immunocytochemical staining was used to trace the proinflammatory cytokines and key transductor of signalling pathways. We also used β‐galactosidase staining, flow cytometry, and cell viability assay to monitor the degenerative index. RESULTS: miR‐640 overexpressed in patients derived degenerative nucleus pulposus tissues and cells. The inflammatory environment promoted miR‐640 expression via NF‐κB signalling pathway. In addition, miR‐640 targeted to LRP1 and enhances NF‐κB signal activity, which built a positive feedback loop. miR‐640 inhibited the expression of β‐catenin and EP300, therefore, restrained WNT signal and induced the degeneration in nucleus pulposus cells. miR‐640 inhibitor treatment exhibited the effects of anti‐inflammation, reverse WNT signalling pathway exhaustion, and remission of degenerative characteristics in vitro. CONCLUSIONS: miR‐640 plays an important role in the degeneration of intervertebral disc and the relative inflammatory microenvironment. It is a promising potential therapeutic target for the low back pain biotherapy. John Wiley and Sons Inc. 2019-07-25 /pmc/articles/PMC6797513/ /pubmed/31343104 http://dx.doi.org/10.1111/cpr.12664 Text en © 2019 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Dong, Wengang Liu, Jun Lv, Yang Wang, Fei Liu, Tao Sun, Siguo Liao, Bo Shu, Zhen Qian, Jixian miR‐640 aggravates intervertebral disc degeneration via NF‐κB and WNT signalling pathway |
title | miR‐640 aggravates intervertebral disc degeneration via NF‐κB and WNT signalling pathway |
title_full | miR‐640 aggravates intervertebral disc degeneration via NF‐κB and WNT signalling pathway |
title_fullStr | miR‐640 aggravates intervertebral disc degeneration via NF‐κB and WNT signalling pathway |
title_full_unstemmed | miR‐640 aggravates intervertebral disc degeneration via NF‐κB and WNT signalling pathway |
title_short | miR‐640 aggravates intervertebral disc degeneration via NF‐κB and WNT signalling pathway |
title_sort | mir‐640 aggravates intervertebral disc degeneration via nf‐κb and wnt signalling pathway |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797513/ https://www.ncbi.nlm.nih.gov/pubmed/31343104 http://dx.doi.org/10.1111/cpr.12664 |
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