Upregulation of Tumor Necrosis Factor α and ADAMTS-5, But Not ADAMTS-4, in Human Intervertebral Cartilage Endplate With Modic Changes
Upregulation of Tumor Necrosis Factor α and ADAMTS-5, But Not ADAMTS-4, in Human Intervertebral Cartilage Endplate With Modic Changes
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DOI：
10.1097/brs.0000000000000362
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发表时间：
2014-06-15
期刊：
影响因子：
3
通讯作者：
Fan, Shun-Wu
中科院分区：
文献类型：
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作者：
Chen, Shuai;Huang, Yue;Fan, Shun-Wu
研究设计。本研究探讨2种ADAMTS在人椎间软骨终板(CEP)中的表达及肿瘤坏死因子α(TNF-α)诱导的核因子κB信号通路的相关机制。 目的。确定哪种类型的 ADAMTS 表达更强烈以及 TNF-α 在 CEP 中的作用。背景数据摘要。 ADAMTS-4和ADAMTS-5被证明在关节软骨和椎间盘退变中至关重要。 CEP是与盘相邻的重要结构。然而，ADAMTS在CEP中的活性尚不清楚。方法。 CEP 是从脊柱手术后的受试者身上获得的，并分为 Modic 改变组或对照组的成员。这些组织的切片用苏木精-伊红、番红 O 染色，并针对 ADAMTS-4、ADAMTS-5 和 TNF-α 进行免疫组织化学染色。通过定量实时聚合酶链反应研究聚集蛋白聚糖、I 型胶原、II 型胶原、X 型胶原、ADAMTS-4、ADAMTS-5 和 TNF-α 的转录水平。此外，在体外培养的牛终板软骨细胞中研究了TNF-α对ADAMTS-5的影响及其潜在机制。结果。我们的数据表明，在 Modic 变化患者的 CEP 中，与细胞外基质蛋白表达相关的退行性变化与 ADAMTS-5 水平升高相关，但与 ADAMTS-4 水平无关。 Modic改变组TNF-α表达水平显着升高，与ADAMTS-5表达增强相关。进一步的体外研究证实，TNF-α可以通过激活培养的牛终板软骨细胞中的核因子κB途径上调ADAMTS-5的表达。结论。我们得出的结论是，TNF-α 和 ADAMTS-5（而非 ADAMTS-4）的上调可能在退行性 CEP 诱发的腰痛中发挥重要作用。
Study Design. This study investigated the expression of 2 types of ADAMTS in human intervertebral cartilage endplate (CEP) and related mechanisms concerning tumor necrosis factor alpha (TNF-alpha)-induced nuclear factor kappa B signaling pathway.Objective. To determine which type of ADAMTS is more strongly expressed and the role of TNF-alpha in CEP.Summary of Background Data. ADAMTS-4 and ADAMTS-5 were proven to be essential in the degeneration of articular cartilage and intervertebral disc. CEP is an important structure adjacent to the disc. However, the activities of ADAMTS in CEP are unclear.Methods. CEPs were obtained from subjects after spinal surgery and categorized as members of either the Modic change group or the control group. Sections of these tissues were stained with hematoxylin-eosin, safranin O, and immunohistochemistry procedures for ADAMTS-4, ADAMTS-5, and TNF-alpha. Transcriptional levels of aggrecan, type I collagen, type II collagen, type X collagen, ADAMTS-4, ADAMTS-5, and TNF-alpha were investigated by quantitative real-time polymerase chain reaction. In addition, the effect of TNF-alpha on ADAMTS-5 and its potential mechanisms are investigated in cultured bovine endplate chondrocytes in vitro.Results. Our data demonstrated that the degenerative changes associated with the expression of extracellular matrix proteins were correlated with increased levels of ADAMTS-5, but not ADAMTS-4, in the CEP of patients with Modic changes. The expression levels of TNF-alpha in the Modic change group were significantly increased, which was correlated with the enhanced expression of ADAMTS-5. Additional in vitro investigation confirmed that TNF-alpha could upregulate the expression of ADAMTS-5 by activating nuclear factor kappa B pathway in cultured bovine endplate chondrocytes.Conclusion. We conclude that the upregulation of TNF-alpha and ADAMTS-5, but not ADAMTS-4, may play an important role in degenerative CEP-induced low back pain.