动态应力介导Wnt/β-catenin—NF-κB信号交联对椎间盘细胞生物学功能的影响及其机制

The causes for intervertebral disc degeneration are complicated and dynamic press stimulus is seemed as one of the important factors. Previous studies found that the expression of NF-κB signal pathway is up-regulated under dynamic press stimulus, which also up-regulated the expression of matrix metalloproteinases (MMP) associated proteins, and the latter can degrade collagen and proteoglycan within the disc, these changes can result in the disc degeneration. In addition, Wnt/Catenin signal pathway is up-regulated during the early stage of disc degeneration, but the correlation between Wnt/Catenin signal pathway and tissue component is still unclear. To date, the mechanism of disc degeneration is still unclear. Based on above papers described, when our research group employed dynamic press to stimulate nucleus pulposus cells, up-regulation of Wnt/Catenin signal pathway also may up-regulate the MMP associated genes and proteins, but the result can be reversed when NF-κB signal pathway was blocked. Thus, we speculate Wnt/Catenin signal pathway involves in the regulation of disc at a fashion similar to NF-κB signal pathway. Our research take the cross-linking between wnt/β-Catenin and NF-κB signal pathways as new breathrough under dynamic press stimulus, and plan to reveal the new mechamism and regulation of disc degeneration. We wish it can provide new experimental basis and idea for its prevention and cure.

椎间盘退变原因复杂，动态应力刺激被认为是重要的因素之一。研究发现在动态应力刺激下，NF-κB信号表达上调并引起MMP等相关蛋白表达增强，后者解降盘内胶原蛋白和蛋白聚糖等，引起椎间盘退变。此外，Wnt/Catenin信号被发现在椎间盘退变的早期上调，但与盘内组织成分的关系仍然不清。但迄今为止，椎间盘退变的机制仍然不是十分清楚。基于以上文献报道，课题组前期在运用动态应力刺激髓核细胞时，在上调Wnt/Catenin信号时，MMP相关基因及蛋白亦显著上调，但阻断NF-κB信号通路后，上述结果和趋势被翻转。由此，我们推测：Wnt/Catenin类似于NF-κB信号对椎间盘的调控，也参与该退变过程。本实验在动态应力刺激条件下，以Wnt/β-Catenin与NF-κB信号通路交联作为新突破点，拟从新角度揭示椎间盘退变的可能机制及其信号调控，以期为其防治提供实验依据和新的思路。

本课题组自获得国家自然基金资助后，课题负责人按照预定的人员安排，对课题研究相关内容进行组织分工，相关课题成员严格认真按照国家自然基金面上项目任务书逐步实施。我们发现在运用动态应力刺激髓核细胞时，随着应力的增大，髓核细胞的活力降低，其相应基因和蛋白表达下降，在高频动态下，该趋势进一步加剧。而在上调Wnt /Catenin信号时MMP相关基因及蛋白显著上调，相应髓核 细胞或体内试验皆表明其相应基因和蛋白表达下降，但在阻断NF-κB信号通路后，上述结果趋势被翻转。表明Wnt/ Catenin类似NF-κB信号对椎间盘的调控，也参与椎间盘的退变过程，起重要调节作用。