Intervertebral disk degeneration (IVDD) contributes to low back pain. Increased cell apoptosis and inflammation, decreased extracellular matrix are associated with IVDD. Nuclear factor-kappa B (NF-κB) signaling pathway and inflammatory cytokines are implicated in the pathophysiology of IVDD. In present study, we established a mechanical stretching stress-stimulated nucleus pulposus (NP) cell model. We knocked down NF-κB p65 by siRNA transfection to inhibit NF-κB and evaluated the effects of NF-κB inhibition on intervertebral disk degeneration. We applied the mechanical stretching stress on NP cells and inhibited NF-κB by siRNA, then evaluated the expression of inflammatory cytokines, matrix metalloproteinase (MMP), aggrecan, collagen II, and monitored viability and apoptosis of NP cells. Mechanical stretching stress induced the expression of TNF-α, IL-1β, NF-κB, MMP-3 and MMP-13, while inhibited the production of aggrecan and collagen II in NP cells. Mechanical stretching stress decreased the cell viability and induced apoptosis in NP cells. Inhibition of NF-κB by siRNA suppressed the production of TNF-α, IL-1β, NF-κB, MMP-3 and MMP-13, while upregulated the expression of aggrecan and collagen II in NP cells. Inhibition of NF-κB by knocking down p65 suppressed over-mechanical stretching stress-induced cell apoptosis and promoted viability in NP cell. Inhibition of NF-κB suppressed inflammation and degeneration of NP cells in IVDD.

中文翻译：

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NF-κB通路对过度机械拉伸应力所致椎间盘炎症和退变的影响

椎间盘退变 (IVDD) 会导致腰痛。细胞凋亡和炎症增加，细胞外基质减少与 IVDD 相关。核因子-κB (NF-κB) 信号通路和炎性细胞因子与 IVDD 的病理生理学有关。在本研究中，我们建立了机械拉伸应力刺激的髓核（NP）细胞模型。我们通过 siRNA 转染敲低 NF-κB p65 以抑制 NF-κB 并评估 NF-κB 抑制对椎间盘退变的影响。我们对 NP 细胞施加机械拉伸应力并通过 siRNA 抑制 NF-κB，然后评估炎性细胞因子、基质金属蛋白酶 (MMP)、聚集蛋白聚糖、胶原蛋白 II 的表达，并监测 NP 细胞的活力和凋亡。机械拉伸应力诱导TNF-α的表达，IL-1β、NF-κB、MMP-3 和 MMP-13，同时抑制 NP 细胞中聚集蛋白聚糖和胶原蛋白 II 的产生。机械拉伸应力降低了 NP 细胞的细胞活力并诱导细胞凋亡。siRNA 对 NF-κB 的抑制抑制了 TNF-α、IL-1β、NF-κB、MMP-3 和 MMP-13 的产生，同时上调了 NP 细胞中聚集蛋白聚糖和胶原蛋白 II 的表达。通过敲低 p65 抑制 NF-κB 可抑制过度机械拉伸应激诱导的细胞凋亡并促进 NP 细胞的活力。NF-κB 的抑制抑制了 IVDD 中 NP 细胞的炎症和退化。IL-1β、NF-κB、MMP-3 和 MMP-13，同时上调 NP 细胞中聚集蛋白聚糖和胶原蛋白 II 的表达。通过敲低 p65 抑制 NF-κB 可抑制过度机械拉伸应激诱导的细胞凋亡并促进 NP 细胞的活力。NF-κB 的抑制抑制了 IVDD 中 NP 细胞的炎症和退化。IL-1β、NF-κB、MMP-3 和 MMP-13，同时上调 NP 细胞中聚集蛋白聚糖和胶原蛋白 II 的表达。通过敲低 p65 抑制 NF-κB 可抑制过度机械拉伸应激诱导的细胞凋亡并促进 NP 细胞的活力。NF-κB 的抑制抑制了 IVDD 中 NP 细胞的炎症和退化。