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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...

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Autores principales: Dong, Wengang, Liu, Jun, Lv, Yang, Wang, Fei, Liu, Tao, Sun, Siguo, Liao, Bo, Shu, Zhen, Qian, Jixian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
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.
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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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