ABSTRACT

Visfatin reportedly induces the expression of proinflammatory cytokines. Severe grades of intervertebral disc disease (IVDD) exhibit higher expression of visfatin than mild ones. However, the direct relationship between visfatin and IVDD remains to be elucidated. This study aimed to clarify whether stimulation of visfatin in IVDD is mediated by IL-6. To investigate the role of visfatin in IVDD, a rat model of anterior disc puncture was established by injecting visfatin or PBS using a 27-gauge needle. Results revealed an obvious aggravation of the histological morphology of IVDD in the visfatin group. On treating human NP cellswith visfatin, the levels of collagenII and aggrecan decreased and those of matrix metallopeptidase 3 and IL-6 gradually increased. A rapid increase in ERK, JNK, and p38 phosphorylation was also noted after visfatin treatment. Compared to those treated with visfatin alone, NP cells pretreated with ERK1/2, JNK, and p38 inhibitors or siRNA targeting p38, ERK, and JNK exhibited a significant suppression of IL-6. Our data represent the first evidence that visfatin promotes IL-6 expression in NP cells via the JNK/ERK/p38-MAPK signalling pathways. Further, our findings suggest epidural fat and visfatin as potential therapeutic targets for controlling IVDD-associated inflammation.

摘要

据报道，内脂素诱导促炎细胞因子的表达。严重级别的椎间盘疾病 (IVDD) 表现出比轻度级别更高的内脂素表达。然而，内脂素和 IVDD 之间的直接关系仍有待阐明。本研究旨在阐明 IVDD 中内脂素的刺激是否由 IL-6 介导。为了研究内脂素在 IVDD 中的作用，通过使用 27 号针头注射内脂素或 PBS 来建立前椎间盘穿刺大鼠模型。结果显示，visfatin组IVDD的组织学形态明显加重。用visfatin处理人NP细胞后，胶原II和聚集蛋白聚糖的水平降低，基质金属肽酶3和IL-6的水平逐渐升高。内脂素处理后还注意到 ERK、JNK 和 p38 磷酸化的快速增加。与单独用内脂素处理的细胞相比，用 ERK1/2、JNK 和 p38 抑制剂或靶向 p38、ERK 和 JNK 的 siRNA 预处理的 NP 细胞表现出对 IL-6 的显着抑制。我们的数据代表了内脂素通过 JNK/ERK/p38-MAPK 信号通路促进 NP 细胞中 IL-6 表达的第一个证据。此外，我们的研究结果表明硬膜外脂肪和内脂素是控制 IVDD 相关炎症的潜在治疗靶点。