椎间盘退变引起的下腰痛已成为国人三大主要伤残疾病之一，但尚无有效防治手段。维持正常椎间盘组织稳态，尤其是无神经环境，能否作为防治椎间盘退变的办法，尚无肯定。我们前期发现椎间盘前体细胞的微环境成分－蛋白多糖（proteoglycans），能支持前体细胞在无神经条件下发挥功能。重要的是，正常间盘无神经环境是受神经导向因子Sema3A高表达而维持，但其在退变中下调，间盘中Sema3A表达具体机制不清？因此，揭示间盘维持无神经的内稳态作用，将对认识和防治间盘退变提供新思路和新方法。本研究在前期基础上，以外侧AF细胞表达神经导向因子Sema3A为新靶点，利用Sema3A/Mohawk条件性敲除小鼠模型，研究其对椎间盘退变中AF细胞和AF组织的作用机制及干预潜能，若成功，将对基础研究和临床产生意义。

Low back pain derived from intervertebral disc degeneration is one of the most three disabled diseases in China, which is still no efficient treatment. Whether the maintenance of the aneural status within the intervertebral disc (IVD) could become the potential therapeutic to IVD remains elusive. The work from our group has identified the components of IVD progenitor cells, proteoglycans, support the progenitor cells in the aneural microenvironment. Importantly, the components have been potentially involved in the Sema3A inhibition of nerve ingrowth to IVD. It is regarded that the AF degeneration/tear undergoes before the NP degeneration, however it is unknown about the mechanism of Sema3A. As such, the investigation of the role of AF in the inhibition of nerve and the endogenous maintenance would facilitate the understanding of IVD degeneration and regeneration modulation. The project will target the expression of Sema3A in the outer AF and use the gene engineering mice (Sema3A/Mohawk) to elucidate the mechanism of Sema3A in IVD degeneration. This will offer new significance to the IVD research and clinical treatment.