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MicroRNA-146a Ameliorates Inflammation via TRAF6/NF-κB Pathway in Intervertebral Disc Cells

BACKGROUND: Intervertebral disc degeneration (IDD) has been widely recognized as a major contributor to low back pain. Accumulating evidence suggests that IDD is linked to various pro-inflammatory cytokines and metabolites. Recently, numerous studies have demonstrated that microRNAs (miRNAs) play a...

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Autores principales: Lv, Feng, Huang, Yingzi, Lv, Wentao, Yang, Longbiao, Li, Feng, Fan, Jingli, Sun, Jianmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308543/
https://www.ncbi.nlm.nih.gov/pubmed/28161709
http://dx.doi.org/10.12659/MSM.898660
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author Lv, Feng
Huang, Yingzi
Lv, Wentao
Yang, Longbiao
Li, Feng
Fan, Jingli
Sun, Jianmin
author_facet Lv, Feng
Huang, Yingzi
Lv, Wentao
Yang, Longbiao
Li, Feng
Fan, Jingli
Sun, Jianmin
author_sort Lv, Feng
collection PubMed
description BACKGROUND: Intervertebral disc degeneration (IDD) has been widely recognized as a major contributor to low back pain. Accumulating evidence suggests that IDD is linked to various pro-inflammatory cytokines and metabolites. Recently, numerous studies have demonstrated that microRNAs (miRNAs) play a pivotal role in the development of most disorders, including degenerative disc diseases. Previous reports have revealed that miRNA-146a (miR-146a) could attenuate neuropathic pain in the spinal cord. The aim of this study was to investigate the role of miR-146a in the inflammatory response of IDD. MATERIAL/METHODS: Quantitative real-time (RT)-PCR was performed to investigate the levels of miR-146a in the PBMCs (peripheral blood mononuclear cells) of patients with IDD. Human nucleus pulposus (NP) cells were transiently transfected with miR-146a mimic; control NP cell transfections lacked miR-146a. Then all NP cells were treated with LPS (10 μM) to induce inflammation. The mRNA levels of miR-146a in NP cells were determined by RT-PCR. In addition, the mRNA and protein expression levels of tumor necrosis factor (TNF), receptor-associated factor 6 (TRAF6), and nuclear factor (NF)-κB in NP cells were evaluated by quantitative RT-PCR and Western blot analysis, respectively. RESULTS: We found that miR-146a was significantly downregulated in the PBMCs of patients. Moreover, overexpression of miR-146a significantly decreased the levels of pro-inflammatory cytokines in LPS-stimulated NP cells. The mRNA and protein levels of TRAF6 and NF-κB were downregulated by miR-146a overexpression. CONCLUSIONS: These results suggest that overexpression of miR-146a could promote IDD through the TRAF/NF-κB pathway. Our findings also highlight miR-146a as a novel possible therapeutic target for IDD.
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spelling pubmed-53085432017-02-24 MicroRNA-146a Ameliorates Inflammation via TRAF6/NF-κB Pathway in Intervertebral Disc Cells Lv, Feng Huang, Yingzi Lv, Wentao Yang, Longbiao Li, Feng Fan, Jingli Sun, Jianmin Med Sci Monit Lab/In Vitro Research BACKGROUND: Intervertebral disc degeneration (IDD) has been widely recognized as a major contributor to low back pain. Accumulating evidence suggests that IDD is linked to various pro-inflammatory cytokines and metabolites. Recently, numerous studies have demonstrated that microRNAs (miRNAs) play a pivotal role in the development of most disorders, including degenerative disc diseases. Previous reports have revealed that miRNA-146a (miR-146a) could attenuate neuropathic pain in the spinal cord. The aim of this study was to investigate the role of miR-146a in the inflammatory response of IDD. MATERIAL/METHODS: Quantitative real-time (RT)-PCR was performed to investigate the levels of miR-146a in the PBMCs (peripheral blood mononuclear cells) of patients with IDD. Human nucleus pulposus (NP) cells were transiently transfected with miR-146a mimic; control NP cell transfections lacked miR-146a. Then all NP cells were treated with LPS (10 μM) to induce inflammation. The mRNA levels of miR-146a in NP cells were determined by RT-PCR. In addition, the mRNA and protein expression levels of tumor necrosis factor (TNF), receptor-associated factor 6 (TRAF6), and nuclear factor (NF)-κB in NP cells were evaluated by quantitative RT-PCR and Western blot analysis, respectively. RESULTS: We found that miR-146a was significantly downregulated in the PBMCs of patients. Moreover, overexpression of miR-146a significantly decreased the levels of pro-inflammatory cytokines in LPS-stimulated NP cells. The mRNA and protein levels of TRAF6 and NF-κB were downregulated by miR-146a overexpression. CONCLUSIONS: These results suggest that overexpression of miR-146a could promote IDD through the TRAF/NF-κB pathway. Our findings also highlight miR-146a as a novel possible therapeutic target for IDD. International Scientific Literature, Inc. 2017-02-05 /pmc/articles/PMC5308543/ /pubmed/28161709 http://dx.doi.org/10.12659/MSM.898660 Text en © Med Sci Monit, 2017 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
spellingShingle Lab/In Vitro Research
Lv, Feng
Huang, Yingzi
Lv, Wentao
Yang, Longbiao
Li, Feng
Fan, Jingli
Sun, Jianmin
MicroRNA-146a Ameliorates Inflammation via TRAF6/NF-κB Pathway in Intervertebral Disc Cells
title MicroRNA-146a Ameliorates Inflammation via TRAF6/NF-κB Pathway in Intervertebral Disc Cells
title_full MicroRNA-146a Ameliorates Inflammation via TRAF6/NF-κB Pathway in Intervertebral Disc Cells
title_fullStr MicroRNA-146a Ameliorates Inflammation via TRAF6/NF-κB Pathway in Intervertebral Disc Cells
title_full_unstemmed MicroRNA-146a Ameliorates Inflammation via TRAF6/NF-κB Pathway in Intervertebral Disc Cells
title_short MicroRNA-146a Ameliorates Inflammation via TRAF6/NF-κB Pathway in Intervertebral Disc Cells
title_sort microrna-146a ameliorates inflammation via traf6/nf-κb pathway in intervertebral disc cells
topic Lab/In Vitro Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308543/
https://www.ncbi.nlm.nih.gov/pubmed/28161709
http://dx.doi.org/10.12659/MSM.898660
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