METHODS: An IL-1β-induced cell inflammation model and a lumbar instability model inducing IDD were established to assess the progression of IDD with or without limonin treatment. We further evaluated MAPK/NF-κB and necroptosis pathways and alterations in the extracellular matrix specific within the disc.
RESULTS: Limonin suppresses inflammation in the nucleus pulposus in vitro by reducing the production of pro-inflammatory markers such as iNOS and COX-2. Limonin reduced the activation of the MAPK/NF-κB signalling pathway and the RIP1/RIP3/MLKL necroptosis pathway in the NP cells. Moreover, limonin delays the IDD progression in the lumbar instability model.
CONCLUSIONS: Limonin could potentially delay IDD by inhibiting NP cell necroptosis and modulating peripheral matrix proteins within the intervertebral disc and is a potential pharmacological research direction for the therapy in patients with IDD.
方法:建立IL-1β诱导的细胞炎症模型和诱导IDD的腰椎不稳定模型,以评估有或没有柠檬苦素治疗的IDD进展。我们进一步评估了MAPK/NF-κB和坏死途径以及椎间盘内特异性细胞外基质的改变。
结果:柠檬苦素通过减少促炎标志物如iNOS和COX-2的产生在体外抑制髓核内的炎症。柠檬苦素降低了NP细胞中MAPK/NF-κB信号通路和RIP1/RIP3/MLKL坏死通路的激活。此外,在腰椎不稳定模型中,柠檬苦素延迟IDD进展。
结论:柠檬苦素可能通过抑制NP细胞凋亡和调节椎间盘周围基质蛋白而延缓IDD,是IDD患者治疗的潜在药理研究方向。