椎间盘同种异体移植已用于临床，并表现出较好的治疗效果，但移植后的椎间盘为何发生退变尚不明确。椎间盘主要经终板获得营养供给，但在终板营养通路建立之前，移植后的椎间盘一直处于无营养供给状态。营养缺失会导致细胞凋亡，进而诱发椎间盘退变。阐明椎间盘移植后终板变化将有可能解开椎间盘移植后的退变机理。在该项目中，我们首先将建立羊腰椎间盘同种异体移植模型，用动态增强MRI研究终板营养通路的重建模式；用UTE-MRI、Micro-CT、SEM-EDX mapping和组织学等研究骨终板和软骨终板的结构变化；最后我们将探讨冷冻保存椎间盘的软骨终板细胞对营养缺乏的耐受情况和以HIF-1α-HMGB1通路为主的凋亡机制。通过该研究，我们将从功能、结构和细胞水平上阐明椎间盘移植后终板营养通路重建模式、终板的结构和功能重构以及对营养缺乏的耐受情况。这些研究将逐步椎间盘移植后的退变机制，为研发新型修复技术奠定基础。

Fresh-frozen intervertebral disc allograft transplantation has been regarded as a new strategy to regenerate the whole degenerated disc with promising clinical outcomes. Nevertheless, mild degeneration of the allograft has been found in some cases after follow-up, which can be attributed to the loss of timely nutrient supply. It is well known that the normal intervertebral disc obtains most of the nutrients through the endplate pathway; but immediately after transplantation, the allograft is immersed in an ischemic environment until the endplate nutritional pathway is reestablished. Loss of nutrient supply will induce the death of disc cells, leading to the presence of intervertebral disc degeneration. Hence, in order to unravel the reestablishment of the endplate nutritional pathway, we will investigate the structural and functional remodeling process of the endplates after disc allografting. In this project, based on the goat model of lumbar intervertebral disc allograft transplantation, we will firstly investigate the reestablishment pattern of the endplate nutritional pathway using the dynamic-enhanced MRI. Then we will perform UTE-MRI, micro-CT scanning, histology and immunochemistry to investigate the structural changes of the bony and cartilaginous endplates. We will also conduct the SEM, EDX mapping and histological staining to observe the micro-structural integration of bony and cartilaginous endplates. Finally, the cells isolated from the cartilaginous endplates of the disc allograft will be exposed to the hypoxia and serum deprivation conditions; the apoptosis of the cartilaginous endplate cells will be evaluated by FACS (Annexin V/PI) and the HIF-1α-HMGB1 based mechanism will be determined by ELISA, PCR and Western Blot studies. All these research data will be very meaningful to uncover the remodeling process of endplates, to determine the resistance of endplates to the poor nutritional condition, and to elucidate the pattern of the reestablished endplate nutritional pathway after disc allografting. Collectively, this project is very meaningful to understand the degenerative mechanism of the disc allograft after transplantation which will be valuable for the development of new reparative approaches for more extensive application in clinics.