腰椎软骨终板退变与腰椎间盘退变及下腰痛密切相关，其发病机制仍不明确。ADAMTS-5是骨关节炎动物模型中最重要的关节软骨细胞外基质蛋白降解酶，也是人关节软骨退变过程中关键的基质蛋白酶，但在腰椎软骨终板退变中的作用未见报道。我们前期研究发现患者退变腰椎软骨终板中ADAMTS-5的表达显著升高，进一步动物模型和细胞学研究表明IL-1β可使ADAMTS-5的表达增加，降解细胞外基质，导致终板退变，提示ADAMTS-5在腰椎软骨终板退变中发挥重要作用。文献表明关节软骨中ADAMTS-5的表达可被IL-1β-NF-kB通路信号调控，并导致关节软骨退变。为此，本研究将以ADAMTS-5条件性基因敲除和基因过表达为基础，从组织、细胞及分子层面分析ADAMTS-5在腰椎终板退变中的作用。并通过NF-kB通路研究IL-1β调节ADAMTS-5的可能机制，为开发以ADAMTS-5为靶点的生物治疗提供理论依据。

Lumbar cartilage endplate degeneration is closely associated with the process of the lumbar intervetebral disc degeneration and may contribute to low back pain. However, its mechanism remains unclear. ADAMTS-5 is the primary aggrecanase responsible for aggrecan degradation in animal models of osteoarthritis, which also plays a key role in human articular cartilage destruction. Yet its role in human lumbar cartilage endplate remains largely unknown. With our efforts on understanding the molecular mechanisms of lumbar cartilage endplate degeneration, we identified upregulation of ADAMTS-5 in degenerated endplate samples. We further successfully generated an lumbar cartilage endplate degeneration animal model by intradiscal injection of IL-1β. And the injection of IL-1β enhanced ADAMTS-5 expression and subsequently caused extracellular matrix degeneration. This observation was further confirmed by our ex vivo data that demonstrated IL-1β induced endplate degeneration via upregulation of ADAMTS-5. Previous study revealed that IL-1β-NF-kB signalling pathway could induce articular cartilage degeneration via upregulation of ADAMTS-5. Based on these findings, we propose to investigate the effect of ADAMTS-5 on lumbar cartilage endplate degeneration using a chondrocyte specific ADAMTS-5 conditional knockout mice, as well as lentivirus mediated ADAMTS-5 gene overexpression. We believe we will have interesting histologic, cytologic and molecuar findings.In addition, we aim to investigate the regulatory mechanism of ADAMTS-5, which may be regulated by IL-1β through the NF-kB signalling pathway. Our study may probably provide a theoretical foundation for targeted biological therapy for the treatment of lumbar cartilage endplate degeneration.