Wang Gangliang, Huang Kangmao, Dong Yangxin, Chen Shuai, Zhang Jianfeng, Wang Jiying, Xie Ziang, Lin Xianfeng, Fang Xiangqiang, Fan Shunwu
Cell Physiol Biochem. 2018;45(3):1252-1269. doi: 10.1159/000487457. Epub 2018 Feb 9.
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.
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.
In CEP cells, Interleukin (IL)-1β 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-κB (NFκB) signalling and thus prevented IL-1β-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.
LY could serve as a potential drug for treating IVD disease.
背景/目的：软骨终板（CEP）退变是导致椎间盘（IVD）退变进而引发腰痛的重要原因。确定可能预防CEP退变的化合物对于预防IVD退变具有重要意义。
首先评估椎间盘退变患者CEP中分解代谢蛋白酶的表达。通过流式细胞术分析和蛋白质印迹法在体外评估石蒜碱（LY）对CEP来源的软骨细胞退变的毒性、功能及潜在机制。还通过高效液相色谱（HPLC）定量分析和组织学分析评估LY在大鼠尾椎间盘退变模型中的浓度和功能。
在CEP细胞中，白细胞介素（IL）-1β上调基质金属蛋白酶（MMP）-3、MMP-13、含血小板反应蛋白基序的解聚素和金属蛋白酶（ADAMTS）-4及ADAMTS-5的表达，这些酶对软骨细胞外基质的降解至关重要。有趣的是，LY通过抑制核因子-κB（NFκB）信号通路抑制这些酶的表达，从而在体外预防IL-1β诱导的终板细胞退变。更重要的是，LY还降低了CEP中MMP-3、MMP-13、ADAMTS-4和ADAMTS-5的表达，并对CEP和髓核（NP）退变均发挥保护作用。除了对基质降解蛋白酶表达的抑制作用外，LY处理还降低了促炎细胞因子的正向调节因子，如巨噬细胞移动抑制因子（MIF）的表达，MIF可由CEP细胞分泌并随后作用于NP细胞。
LY可作为治疗IVD疾病的潜在药物。
