The inflammatory cytokine tumor necrosis factor alpha (TNFα) is considered to play a key role in the pathogenesis of intervertebral disc disease. To evaluate the importance of this cytokine we examined the inflammatory environment and spinal phenotype of 9-month-old human TNFα overexpressing transgenic (hTNFα-TG) mice. The mice evidenced increased circulating levels of interleukin-1β (IL-1β), IL-2, keratinocyte chemoattractant/human growth-regulated oncogene (KC/GRO), and monocyte chemoattractant protein-1 (MCP-1) along with thinning of the cortical and trabecular vertebral bone. Surprisingly, although the nucleus pulposus (NP) of these mice was intact and healthy, the caudal annulus fibrosus (AF) evidenced robust cell death and immune cell infiltration. Despite these differences, there were no obvious alterations in the collagen or aggrecan content in the NP and AF. However, there was a reduction in cartilage oligomeric matrix protein (COMP), suggesting destabilization of the AF matrix. Microarray analysis of the NP from hTNFα-TG mice cells revealed minimal changes in global gene expression. These findings lend support to the notion that NP tissue is isolated from systemic inflammation. In contrast, the severe AF phenotype suggests that systemic inflammation interferes with AF health, predisposing discs to herniation as opposed to directly causing NP degeneration. © 2020 American Society for Bone and Mineral Research.

中文翻译：

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长期全身性暴露TNFα对椎间盘纤维环和髓核健康的差异作用。

炎性细胞因子肿瘤坏死因子α（TNFα）被认为在椎间盘疾病的发病机理中起关键作用。为了评估这种细胞因子的重要性，我们检查了9个月大的人类TNFα过表达转基因（hTNFα-TG）小鼠的炎症环境和脊髓表型。小鼠证明白细胞介素-1β（IL-1β），IL-2，角质形成细胞趋化因子/人类生长调节癌基因（KC / GRO）和单核细胞趋化因子蛋白1（MCP-1）的循环水平增加，并且它们的变薄。皮质和小梁椎骨。出人意料的是，尽管这些小鼠的髓核（NP）完整且健康，但尾纤维环（AF）却显示出强大的细胞死亡和免疫细胞浸润。尽管有这些差异，NP和AF中胶原蛋白或聚集蛋白聚糖含量没有明显变化。但是，软骨寡聚基质蛋白（COMP）减少，提示AF基质不稳定。对来自hTNFα-TG小鼠细胞的NP的微阵列分析显示，全局基因表达的变化很小。这些发现支持了NP组织与全身性炎症分离的观点。相反，严重的房颤表型提示全身性炎症会干扰房颤的健康，使椎间盘突出，而不是直接导致NP变性。©2020美国骨骼和矿物质研究学会。对来自hTNFα-TG小鼠细胞的NP的微阵列分析显示，全局基因表达的变化很小。这些发现支持了将NP组织与全身性炎症隔离的观点。相反，严重的房颤表型提示全身性炎症会干扰房颤的健康，使椎间盘容易发生突出而不是直接导致NP变性。©2020美国骨骼和矿物质研究学会。对来自hTNFα-TG小鼠细胞的NP的微阵列分析显示，全局基因表达的变化很小。这些发现支持了NP组织与全身性炎症分离的观点。相反，严重的房颤表型提示全身性炎症会干扰房颤的健康，使椎间盘容易发生突出而不是直接导致NP变性。©2020美国骨骼和矿物质研究学会。