Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/117527
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Type: Journal article
Title: High amplitude and low frequency cyclic mechanical strain promotes degeneration of human nucleus pulposus cells via the NF-κB p65 pathway
Other Titles: High amplitude and low frequency cyclic mechanical strain promotes degeneration of human nucleus pulposus cells via the NF-kappaB p65 pathway
Author: Wang, S.
Li, J.
Tian, J.
Yu, Z.
Gao, K.
Shao, J.
Li, A.
Xing, S.
Dong, Y.
Li, Z.
Gao, Y.
Wang, L.
Xian, C.J.
Citation: Journal of Cellular Physiology, 2018; 233(9):7206-7216
Publisher: Wiley
Issue Date: 2018
ISSN: 0021-9541
1097-4652
Statement of
Responsibility: 
Shengjie Wang, Jie Li, Jiwei Tian, Zhenghong Yu, Kun Gao, Jia Shao, Ang Li, Shuai Xing, Yonghui Dong, Zhiyong Li, Yanzheng Gao, Liping Wang, Cory J. Xian
Abstract: Disc degeneration alters the structure and function of intervertebral discs and is the basis of spinal degenerative diseases. To establish the molecular mechanism of intervertebral disc degeneration caused by mechanical strain, this study examined the effects of different amplitude (3%, 9%, 19%) cyclic mechanical strain (CMS) at a low frequency (0.01 Hz) on the secretion of cartilage extracellular matrix, expression of inflammatory cytokines and catabolic proteases, and activation of NF-κB signaling pathway in human nucleus pulposus cells. We also investigated effects of low frequency and high amplitude (19%) CMS on degeneration of human nucleus pulposus cells in the presence or absence of p65 inhibitor, p65 silencing shRNA, or p65 overexpression. While 3% CMS did not significantly decrease aggrecan or type II collagen expression, or increase TNF-α, IL-1β, IL-6 expression, 9% and 19% CMS showed the significant effects. Low frequency and high amplitude (19%) CMS was found to promote p65 activation in human nucleus pulposus cells, and IL-1β was found to promote p65 nuclear translocation though IκB kinase phosphorylation. Furthermore, degeneration process of nucleus pulposus cells was found attenuated in the presence of p65 inhibitor or p65 silencing shRNA, but promoted with p65 overexpression. These data suggest that high amplitude and low frequency CMS could promote degeneration of human nucleus pulposus cells significantly via the NF-κB p65 pathway. Our findings have uncovered the effect of CMS on human nucleus pulposus cell degeneration and have identified a previously unknown intrinsic underlying mechanism.
Keywords: Cyclic mechanical strain; intervertebral disc degeneration; NF-κB pathway; nucleus pulposus cells
Rights: © 2018 Wiley Periodicals, Inc.
RMID: 0030102914
DOI: 10.1002/jcp.26551
Grant ID: http://purl.org/au-research/grants/nhmrc/1094606
http://purl.org/au-research/grants/arc/FT140101152
http://purl.org/au-research/grants/nhmrc/1042105
Appears in Collections:Medicine publications

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