MyD88-dependent Toll-like receptor 4 signal pathway in intervertebral disc degeneration

MyD88-dependent Toll-like receptor 4 signal pathway in intervertebral disc degeneration

Lower back pain (LBP) is a common and remitting problem. One of the primary causes of LBP is thought to be degeneration of the intervertebral disc (IVD). The aim of the present study was to investigate the role of the myeloid differentiation primary-response protein 88 (MyD88)-dependent Toll-like re...

Full description

Bibliographic Details
Main Authors: Qin, Chuqiang, Zhang, Bo, Zhang, Liang, Zhang, Zhi, Wang, Le, Tang, Long, Li, Shuangqing, Yang, Yixi, Yang, Fuguo, Zhang, Ping, Yang, Bo
Format: Online
Language:English
Published: D.A. Spandidos 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950663/
id pubmed-4950663
recordtype oai_dc
spelling pubmed-49506632016-07-21 MyD88-dependent Toll-like receptor 4 signal pathway in intervertebral disc degeneration Qin, Chuqiang Zhang, Bo Zhang, Liang Zhang, Zhi Wang, Le Tang, Long Li, Shuangqing Yang, Yixi Yang, Fuguo Zhang, Ping Yang, Bo Articles Lower back pain (LBP) is a common and remitting problem. One of the primary causes of LBP is thought to be degeneration of the intervertebral disc (IVD). The aim of the present study was to investigate the role of the myeloid differentiation primary-response protein 88 (MyD88)-dependent Toll-like receptor 4 (TLR4) signal pathway in the mechanism of IVD degeneration. IVD nucleus pulposus cells isolated and cultured from the lumbar vertebrae of Wistar rats were stimulated by various doses of lipopolysaccharide (LPS; 0.1, 1, 10 and 100 µg/ml) to simulate IVD degeneration. Cells were rinsed and cultured in serum-free Dulbecco's modified Eagle's medium/F12. Reverse transcription-quantitative polymerase chain reaction was used to determine the levels of TLR4, MyD88, tumor necrosis factor α (TNFα), and interleukin-1β (IL-1β) mRNA expression after 1, 3, 6, 9 and 12 h of incubation. Additionally, western blot and enzyme-linked immunosorbent assay analyses were used to determine the levels of TLR4, MyD88, TNFα, and IL-1β protein expression after 24, 48 and 72 h of incubation. The levels of TLR4, MyD88, TNFα and IL-1β mRNA all increased in the cells stimulated by 10 µg/ml LPS at 3, 6 and 9 h (all P<0.001). Furthermore, the levels of TLR4, MyD88, TNFα and IL-1β protein all increased at 24, 48 and 72 h (all P<0.001). Additionally, the mRNA and protein levels of TLR4, MyD88, TNFα and IL-1β increased significantly in the cells stimulated by 1, 10 and 100 µg/ml LPS compared with the control group, and reached a peak in the 10 µg/ml LPS group (all P<0.001). These results suggest that the MyD88-dependent TLR4 signal pathway is a target pathway in IVD degeneration. This pathway is time phase- and dose-dependent, and when activated can lead to the release of inflammatory factors that participate in IVD degeneration. D.A. Spandidos 2016-08 2016-06-06 /pmc/articles/PMC4950663/ /pubmed/27446251 http://dx.doi.org/10.3892/etm.2016.3425 Text en Copyright: © Qin et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Qin, Chuqiang
Zhang, Bo
Zhang, Liang
Zhang, Zhi
Wang, Le
Tang, Long
Li, Shuangqing
Yang, Yixi
Yang, Fuguo
Zhang, Ping
Yang, Bo
spellingShingle Qin, Chuqiang
Zhang, Bo
Zhang, Liang
Zhang, Zhi
Wang, Le
Tang, Long
Li, Shuangqing
Yang, Yixi
Yang, Fuguo
Zhang, Ping
Yang, Bo
MyD88-dependent Toll-like receptor 4 signal pathway in intervertebral disc degeneration
author_facet Qin, Chuqiang
Zhang, Bo
Zhang, Liang
Zhang, Zhi
Wang, Le
Tang, Long
Li, Shuangqing
Yang, Yixi
Yang, Fuguo
Zhang, Ping
Yang, Bo
author_sort Qin, Chuqiang
title MyD88-dependent Toll-like receptor 4 signal pathway in intervertebral disc degeneration
title_short MyD88-dependent Toll-like receptor 4 signal pathway in intervertebral disc degeneration
title_full MyD88-dependent Toll-like receptor 4 signal pathway in intervertebral disc degeneration
title_fullStr MyD88-dependent Toll-like receptor 4 signal pathway in intervertebral disc degeneration
title_full_unstemmed MyD88-dependent Toll-like receptor 4 signal pathway in intervertebral disc degeneration
title_sort myd88-dependent toll-like receptor 4 signal pathway in intervertebral disc degeneration
description Lower back pain (LBP) is a common and remitting problem. One of the primary causes of LBP is thought to be degeneration of the intervertebral disc (IVD). The aim of the present study was to investigate the role of the myeloid differentiation primary-response protein 88 (MyD88)-dependent Toll-like receptor 4 (TLR4) signal pathway in the mechanism of IVD degeneration. IVD nucleus pulposus cells isolated and cultured from the lumbar vertebrae of Wistar rats were stimulated by various doses of lipopolysaccharide (LPS; 0.1, 1, 10 and 100 µg/ml) to simulate IVD degeneration. Cells were rinsed and cultured in serum-free Dulbecco's modified Eagle's medium/F12. Reverse transcription-quantitative polymerase chain reaction was used to determine the levels of TLR4, MyD88, tumor necrosis factor α (TNFα), and interleukin-1β (IL-1β) mRNA expression after 1, 3, 6, 9 and 12 h of incubation. Additionally, western blot and enzyme-linked immunosorbent assay analyses were used to determine the levels of TLR4, MyD88, TNFα, and IL-1β protein expression after 24, 48 and 72 h of incubation. The levels of TLR4, MyD88, TNFα and IL-1β mRNA all increased in the cells stimulated by 10 µg/ml LPS at 3, 6 and 9 h (all P<0.001). Furthermore, the levels of TLR4, MyD88, TNFα and IL-1β protein all increased at 24, 48 and 72 h (all P<0.001). Additionally, the mRNA and protein levels of TLR4, MyD88, TNFα and IL-1β increased significantly in the cells stimulated by 1, 10 and 100 µg/ml LPS compared with the control group, and reached a peak in the 10 µg/ml LPS group (all P<0.001). These results suggest that the MyD88-dependent TLR4 signal pathway is a target pathway in IVD degeneration. This pathway is time phase- and dose-dependent, and when activated can lead to the release of inflammatory factors that participate in IVD degeneration.
publisher D.A. Spandidos
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950663/
_version_ 1613611714352250880

Similar Items