椎间盘退变及其继发的系列疾病是导致腰痛的重要原因。从分子水平深入研究椎间盘退变的关键机制，有利于开辟椎间盘退变及腰痛的治疗新途径。我们前期结果发现：①在人退变椎间盘手术标本中，警报素（Alarmins）S100A8表达明显升高，并与基质降解酶MMP1/13及炎性因子TNF-α等表达水平呈正相关；②S100A8/A9处理髓核细胞后，基质降解酶MMP-1/13和炎性因子IL-6表达升高，而基质成分II型胶原含量降低，且该作用与细胞膜受体TLR4及NF-κB信号通路的激活有关。在此基础上，本项目拟开展以下研究：在人椎间盘手术标本中，明确S100A8/A9与椎间盘退变的相关性；在体内外实验中明确S100A8/A9对椎间盘退变的作用模式和调控机制；在动物模型中验证S100A8/A9对椎间盘退变及腰痛的作用和机制。通过本项目的实施，为椎间盘退变及腰痛的生物学治疗提供潜在的新靶点。

Intervertebral disc degeneration (IVDD) and related diseases are primary causes for low back pain (LBP). Intensive study on the molecular mechanisms of key markers is an important way to identify new therapeutic strategy for IVDD and LBP. In preliminary study, we observed that alarmins S100A8 expression was elevated in human degenerative disc tissues, which correlated with the expression of MMP1/13 and TNF-α. In nucleus pulposus cells, S100A8/A9 up-regulated the expression of MMP-1/13 and IL-6, while down-regulated Collagen II expression. We further found S100A8/A9-induced effects were related with toll-like receptor-4 and activation of the NF-κB signaling pathway. On this basis, we designed the current study: confirm the relationship between S100A8/A9 and IVDD in human disc samples; explore the function and mechanism of S100A8/A9 in disc degeneration in vitro and in vivo; validate the role of S100A8/A9 in disc degeneration and low back pain using an IVDD animal model. This research will explore the mechanism of S100A8/A9 inducing disc degeneration and low back pain, which may provide a novel therapeutic target for the treatment of IVDD and LBP.