慢性下腰痛是临床极为常见的疾病，椎间盘退变（IVDD）被认为是引起下腰痛的重要原因之一。研究发现聚集蛋白聚糖减少引起髓核细胞外基质(ECM)合成与分解代谢的失衡是IVDD的重要机制，含I型血小板结合蛋白基序的解聚蛋白样金属蛋白酶(ADAMTS)是一种新发现的可降解ECM聚集蛋白聚糖的蛋白酶，研究已经证明ADAMTS家族在骨性关节炎的发病过程中起到重要作用，我们的预实验发现，ADAMTS-1在正常大鼠和人的椎间盘中有微量表达，在退变的椎间盘中表达明显升高；TNF-α与IL-1β可上调ADAMTS-1的表达，可增加ADAMTS-1启动子活性，并可激活NF-κB传导通路。在上述预实验的基础上，我们提出假设：TNF-α与IL-1β通过激活NF-κB信号通路上调ADAMTS-1表达加速IVDD的发生。该研究为延缓IVDD进展提供可能的分子生物学依据，为腰痛患者的早期治疗提供新的选择。

Chronic low back pain affects a lot of people in their lives. The primary cause of low back pain is degeneration of the intervertebral discs. Intervertebral disc degeneration (IVDD) is linked to loss of extracellular matrix (ECM), particularly the early loss of aggrecan. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family that cleave aggrecan in vitro are likely to play a role in aggrecan degradation and subsequent disk degeneration as in the pathogenesis of osteoarthritis. According to our previous studies, ADAMTS-1 is expressed at a very low level in tissues of the normal intervertebral disk (in adult rat and human). ADAMTS-1 expression is significantly elevated in degenerative disk. It has been reported that during disk degeneration, in addition to infiltrating immune cells, resident nucleus pulposus(NP) and annulus fibrosus(AF) cells produce high levels of the cytokines TNF-α and IL-1β. We found that there was a dose-dependent increase in ADAMTS-1 mRNA expression by the cytokines treatment. Both cytokines significantly increased the ADAMTS-1 promoter activity. We also found that cytokines modulated ADAMTS-1 expression by NF-κB signaling in rat NP cells. Surprisingly, despite the importance of these aggrecanases in the pathogenesis of osteoarthritis and disk disease, only few studies have investigated regulation of ADAMTS-1 transcription in NP cells, and none have used promoter analysis. Above all, these observations beg the question of how TNF-α and IL-1β control the expression of ADAMTS-1 and what is their relative contribution in NP cells in terms of aggrecan degradation. According to our previous study, we hypothesis that TNF-α and IL-1β associated with ADAMTS-1 expression in degenerative disk through NF-κB pathway. Targeting these enzymes may be a possible future therapeutic strategy for the prevention of intervertebral disc degeneration and its associated morbidity.