Inflammatory and catabolic signalling in intervertebral discs: the roles of NF-κB and MAP kinases.
Inflammatory and catabolic signalling in intervertebral discs: the roles of NF-κB and MAP kinases.
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DOI：
10.22203/ecm.v023a08
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发表时间：
2012-02
影响因子：
3.1
通讯作者：
K. Wuertz;N. Vo;D. Kletsas;N. Boos
中科院分区：
文献类型：
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作者：
K. Wuertz;N. Vo;D. Kletsas;N. Boos
疼痛性椎间盘疾病的特征不仅在于合成代谢（即基质合成）和分解代谢（即基质降解）过程之间的不平衡，而且还在于炎症机制。基质金属蛋白酶和炎症因子的表达和合成增加是由特定信号转导介导的，特别是核因子-κB (NF-kB) 和丝裂原激活蛋白激酶 (MAPK) 介导的途径。 NF-kB 和 MAPK 已被确定为几种肌肉骨骼疾病（例如骨关节炎）中炎症和分解代谢的主要调节因子，最近越来越多的证据支持这些信号通路在疼痛性椎间盘疾病中的重要性。随着不断研究利用体外和体内模型系统来阐明这些通路在椎间盘退变中的作用，在不久的将来，有可能专门针对这些主要炎症/分解代谢信号通路来治疗疼痛的退行性椎间盘疾病。从这个角度来看，我们的目的是总结有关椎间盘疾病 (IDD) 炎症和分解代谢分子途径的当前知识状况，并详细描述椎间盘细胞中 NF-kB 和 MAP 激酶介导的信号转导。此外，我们将讨论使用针对这些途径的药物抑制剂治疗 IDD 的新兴分子治疗模式。
Painful intervertebral disc disease is characterised not only by an imbalance between anabolic (i.e., matrix synthesis) and catabolic (i.e., matrix degradation) processes, but also by inflammatory mechanisms. The increased expression and synthesis of matrix metalloproteinases and inflammatory factors is mediated by specific signal transduction, in particular the nuclear factor-kappaB (NF-kB) and mitogen-activated protein kinase (MAPK)-mediated pathways. NF-kB and MAPK have been identified as the master regulators of inflammation and catabolism in several musculoskeletal disorders (e.g., osteoarthritis), and recently growing evidence supports the importance of these signalling pathways in painful disc disease. With continuing research exploiting in vitro and in vivo model systems to elucidate the roles of these pathways in disc degeneration, it may be possible in the near future to specifically target these major inflammatory / catabolic signalling pathways to treat painful degenerative disc disease. In this perspective, we aim to summarise the current state of knowledge concerning the inflammatory and catabolic molecular pathways of intervertebral disc disease (IDD), with a detailed description of NF-kB and MAP kinase-mediated signal transduction in disc cells. Furthermore, we will discuss the emerging novel molecular treatment modalities for IDD using pharmacological inhibitors targeting these pathways.