High amplitude and low frequency cyclic mechanical strain promotes degeneration of human nucleus pulposus cells via the NF-κB p65 pathway
High amplitude and low frequency cyclic mechanical strain promotes degeneration of human nucleus pulposus cells via the NF-κB p65 pathway
复制标题
高振幅和低频循环机械应变通过 NF-kappa B p65 途径促进人髓核细胞变性
DOI：
10.1002/jcp.26551
复制
发表时间：
2018-09-01
影响因子：
5.6
通讯作者：
Xian, Cory J.
中科院分区：
文献类型：
--
作者：
Wang, Shengjie;Li, Jie;Xian, Cory J.
椎间盘退变改变了椎间盘的结构和功能，是脊柱退行性疾病的基础。为探讨机械应变引起椎间盘退变的分子机制，本研究观察了低频（0.01Hz）不同幅度（3%、9%、19%）的周期性机械应变（CMS）对人髓核细胞分泌软骨细胞外基质、炎性细胞因子和分解代谢蛋白酶表达以及NF-B信号通路激活的影响。我们还研究了在存在或不存在p65抑制剂、p65沉默shRNA或p65过表达的情况下，低频率和高振幅（19%）CMS对人髓核细胞变性的影响。3%CMS对聚集蛋白聚糖和Ⅱ型胶原表达无明显抑制作用，对TNF-α、IL-1、IL-6表达无明显促进作用，而9%CMS和19%CMS对TNF-α、IL-1、IL-6表达有明显抑制作用。低频率高振幅（19%）CMS可促进人髓核细胞中p65的活化，IL-1可通过IB激酶磷酸化促进p65核转位。p65抑制剂和p65沉默shRNA均能抑制髓核细胞的退变，而p65过表达则能促进髓核细胞退变。这些数据表明，高振幅和低频率CMS可以促进人髓核细胞的退变，通过NF-B p65通路显着。我们的研究结果揭示了CMS对人类髓核细胞变性的影响，并确定了一个以前未知的内在潜在机制。
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 (0.01Hz) on the secretion of cartilage extracellular matrix, expression of inflammatory cytokines and catabolic proteases, and activation of NF-B 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-, IL-1, 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-1 was found to promote p65 nuclear translocation though IB 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-B 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.