Andrographolide prevents human nucleus pulposus cells against degeneration by inhibiting the NF-κB pathway
Andrographolide prevents human nucleus pulposus cells against degeneration by inhibiting the NF-κB pathway
复制标题
穿心莲内酯通过抑制 NF-kappaB 通路来防止人髓核细胞变性。
DOI：
10.1002/jcp.27650
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发表时间：
2019-06-01
影响因子：
5.6
通讯作者：
Zheng, Li
中科院分区：
文献类型：
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作者：
Liu, Jianwei;Jiang, Tongmeng;Zheng, Li
椎间盘退变（IDD）是最常见的脊柱疾病之一，其病理特征是过度的细胞凋亡和促炎因子的产生。针对髓核退变的药物靶向治疗可能在IDD治疗中有希望，但它受到药物不良副作用和非特异性的限制。在这项研究中，我们使用了一种天然化合物，穿心莲（ANDRO），这已被广泛用于干预炎症和凋亡性疾病的研究，在NP变性的基础上，IDD患者衍生的NP细胞的脂多糖（LPS）治疗的变性保存。结果表明，LPS处理后NP细胞的变性状态得到维持，表现为高的凋亡率和变性和炎症介质的表达。ANDRO逆转了LPS引起的NP细胞变性的作用，并保持了NP细胞的表型，如流式细胞术、变性介质（ADAMTS 4和ADAMTS 5）、炎症因子（COX 2、PGE 2、MMP-13和MMP-3）、NP细胞生物标志物（SOX 9、ACAN和COL 2A 1）表达和糖胺聚糖分泌所示。我们还发现ANDRO处理中活化的B细胞的核因子κ轻链增强子（NF-κ B）通路参与，表明ANDRO通过抑制NF-κ B通路来防止NP细胞的LPS保存的变性。本研究可为碘缺乏病的临床用药提供参考。
Intervertebral disc degeneration (IDD) is among the most common spinal disorders, pathologically characterized by excessive cell apoptosis and production of proinflammatory factors. Pharmacological targeting of nucleus pulposus (NP) degeneration may hold promise in IDD therapy, but it is limited by adverse side effects and nonspecificity of drugs. In this study, we used a natural compound, andrographolide (ANDRO), which has been widely used to intervene inflammatory and apoptotic diseases in the investigation of NP degeneration based on IDD-patients-derived NP cells by lipopolysaccharide (LPS) treatment for the preservation of degeneration. The results showed that LPS maintained the degeneration status of NP cells as evidenced by a high apoptosis rate and the expression of degenerative and inflammatory mediators after LPS treatment. ANDRO reversed the effects of LPS-caused degeneration of NP cells and maintained the phenotype of NP cells, as demonstrated by flow cytometry, degenerative mediators (ADAMTS4 and ADAMTS5), inflammatory factors (COX2, PGE2, MMP-13, and MMP-3), biomarkers of NP cells (SOX9, ACAN, and COL2A1) expressions, and glycosaminoglycan secretion. We also found the involvement of the nuclear factor kappa-light-chain-enhancer of the activated B cells (NF-kappa B) pathway in ANDRO treatment, indicating that ANDRO prevented the LPS-preserved degeneration of NP cells by inhibiting the NF-kappa B pathway. This study may provide a reference for clinic medication of IDD therapy.