NF-κB信号通路调控Asporin在椎间盘退变中的作用及分子机制研究

椎间盘退变是临床常见病，其机制仍未完全阐明，如何延缓椎间盘退变是国内外基础和临床研究的热点。本课题组前期发现NF-κB信号活化和异常表达与椎间盘退变相关。前期实验采用基因芯片分析了正常和退变的椎间盘表达谱，通过信号通路分析，捕获了NF-κB信号通路和Asporin作为分子靶点。进一步分析发现Asporin启动子序列中存在2个NF-κB的结合位点。本研究的中心假说是NF-κB信号通路在转录水平调控Asporin的表达，参与椎间盘退变。因此，本研究拟采用基因转染、Westernblot、荧光定量PCR等方法在细胞和临床标本中探讨NF-κB信号通路调控Asporin启动子的表达，进而控制Asporin蛋白及mRNA合成，参与椎间盘退变的作用及分子机制，并用动物模型加以验证，评估它们是否可以成为有效延缓椎间盘退变的有效靶标。我们相信本课题的研究成果将为研发有效及安全的治疗手段提供理论与实验基础。

The intervertebral disc degeneration (IVDD) is a common disorder with high morbidity, but its molecular pathogenesis and underlying mechanisms have not been fully elucidated. Our previous studies have found that the activation and abnormal expression of NF-κB signaling pathway were associated with IVDD. In our preliminary experiments, the mechanisms of IVDD were assessed by gene microarray, gene ontology, and pathway analysis; we have found that the NF-κB signaling pathway and Asporin play an important role in IVDD. Moreover, we validated these results in clinical specimens using qRT-PCR. Further analysis has revealed that two NF-κB binding sites exist in the promoter sequence of Asporin gene. Based on previously reports and our preliminary data, we hypothesized that NF-κB regulates Asporin, which is involved in IVDD development and progression. The present project is designed to investigate the role of NF-κB and Asporin in IVDD both in vitro and in vivo, using state-of-the-art cell and molecular biology techniques and cutting-edge IVDD models. Upon completion of the proposed studies, we will provide a basis for future research to develop effective and safe therapy for IVDD.