期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 45, 期 3, 页码 1252-1269出版社
KARGER
DOI: 10.1159/000487457
关键词
Intervertebral disc degeneration; Lycorine; Cartilaginous endplate; Interleukin-1 beta; Macrophage-inhibitory factor; Matrix-degrading protease
资金
- National Nature Science Fund of China [81472064, 81601924]
- Natural Science Fund of Zhejiang Province [Z15H060002]
- funds of science and technology department of Zhejiang Province [2009C03014-1]
- Project of Health and Family Planning Commission of Zhejiang province [2015KYA133, 2017KY087]
- Project of Education Department of Zhejiang Province [Y201017108]
Background/Aims: Cartilaginous endplate (CEP) degeneration is an important cause for intervertebral disc (IVD) degeneration that leads to low-back pain. The identification of compounds that may prevent CEP degeneration is of interest for the prevention of IVD degeneration. Methods: Catabolic protease expression in the CEP of disc degeneration patients was first assessed. The toxicity, function and underlying mechanism of lycorine (LY) on CEP-derived chondrocytes degeneration were assessed in vitro by flow cytometry analysis and western blotting. The concentration and function of LY in rat-tail disc-degeneration models were also assessed by HPLC (High Performance Liquid Chromatography) quantification and histological analysis. Results: In CEP cells, Interleukin (IL)-1 beta upregulated the expression of matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5 that is critical for the degradation of cartilage extracellular matrix. Interestingly, LY suppressed the expression of these enzymes via the inhibition of nuclear factor-kappa B (NF kappa B) signalling and thus prevented IL-1 beta-induced endplate cell degeneration in vitro. More importantly, LY also reduced the expression of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 in CEP and exerted a protective effect on both CEP and nucleus pulposus (NP) degeneration. In addition to its inhibitory effect on matrix-degrading protease expression, LY treatment also reduced positive regulators of proinflammatory cytokines, such as MIF, which can be secreted by CEP cells and subsequently target NP cells. Conclusion: LY could serve as a potential drug for treating IVD disease. (C) 2018 The Author(s) Published by S. Karger AG, Basel
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