非特异性腰痛占腰痛的90%，是常见健康问题，文献与申请人前期研究证实退变过程中软骨终板硬化是其发生的重要原因。但终板硬化的发生机制不清。预实验初步发现，终板硬化过程中，CD31+EMCN+血管新生，该类血管被认为是偶联成骨作用的关键；同时，终板内巨噬细胞发生衰老，分泌IL-10增多，可促进体外血管内皮细胞成管和JAK1及STAT3磷酸化。据此我们提出假说：衰老巨噬细胞特征性分泌IL-10增多，激活JAK1/STAT3通路介导血管新生，导致终板硬化和腰痛发生。本研究拟利用细胞模型、患者和小鼠终板标本，探究巨噬细胞衰老在终板血管新生、硬化和腰痛发生中的作用；证明清除衰老细胞或巨噬细胞可缓解/逆转该作用；进一步验证衰老巨噬细胞特征性分泌IL-10增多，激活JAK1/STAT3通路是重要的分子机制。本研究将从巨噬细胞衰老介导的免疫-血管沟通这个新视点揭示终板硬化的发生机制，为腰痛的防治提供新思路。

Non-specific low back pain (NLBP) that accounts for 90% of low back pain, is a common health problem. Literature and the applicant has previously confirmed that the sclerosis of the cartilage endplate is an important cause of NLBP. But the mechanism of endplate sclerosis is unclear. Our preliminary data showed the angiogenesis of CD31+ EMCN+ blood vessels into the sclerotic endplate, which is considered as the key to coupling osteogenesis; meanwhile, macrophage senescence occurred during endplate sclerosis; the Increased secretion of IL-10 by senescent macrophages promoted the tube formation of vascular endothelial cells and phosphorylation of JAK1 and STAT3. Hence, we hypothesize: senescent macrophages secrete IL-10 which activates the JAK1/STAT3 pathway to promote angiogenesis, leading to endplate sclerosis and NLBP. To demonstrate our hypothesis, we intends to use in vitro cell models, pathological endplate specimens of patients and mouse model to clarify the role of macrophage senescence in endplate angiogenesis, sclerosis and spinal pain; clearance of senescent cells or macrophages can alleviate/reverse this effect; further, we combine qRT-PCR, ELISA and specific neutralizing antibodies or inhibitors to verify the activation of JAK1/STAT3 pathway by senescent macrophages-secreated IL-10 is the critical molecular mechanism. This study will unveil a new perspective of macrophage senescence-mediated immune-vascular communication to reveal the mechanism of endplate sclerosis and provide new ideas for the prevention and treatment of endplate sclerosis-related NLBP.