Department of Orthopaedic Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
Chin Med J (Engl). 2009 Oct 20;122(20):2483-8.
The most significant biological change in intervertebral disc degeneration is the decrease of chondrocyte specific gene and protein expression of Sox9 and collagen type II. Interleukin-1 (IL-1) is not expressed in the normal intervertebral disc tissue but increases in the degenerated intervertebral disc tissue. This suggests that IL-1 may play a role in regulation of the expression of Sox9 and collagen type II.
Human intervertebral disc cells were isolated and cultured. Sox9 and collagen type II expression during treatment with IL-1, with or without the nuclear factor-kappaB (NF-kappaB) activity inhibitor curcumin, were detected by using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, and the activity of the NF-kappaB signaling pathway was detected by the electrophoretic mobility shift assay (EMSA).
IL-1 lowered the mRNA level and protein expression of Sox9 and collagen type II in the cultured intervertebral disc cells in a dose dependent manner (P < 0.05), and this effect was attenuated by curcumin. Curcumin alone had no effect on Sox9 and collagen type II expression (P > 0.05). IL-1 at concentrations of 0.1 ng/ml, 1 ng/ml and 10 ng/ml could stimulate the activity of NF-kappaB in the intervertebral disc cells in a dose dependent manner (P < 0.05) that was inhibited by curcumin.
We demonstrated the previously unknown function of IL-1 in inhibiting Sox9 and collagen type II via NF-kappaB in the intervertebral disc cells. This inhibition can be attenuated by curcumin, which is an effective NF-kappaB activity inhibitor.
椎间盘退变过程中最显著的生物学变化是软骨细胞特异性基因 Sox9 和胶原 II 表达减少。白细胞介素-1（IL-1）在正常椎间盘组织中不表达，但在退变的椎间盘组织中增加。这表明 IL-1 可能在 Sox9 和胶原 II 表达的调节中发挥作用。
分离培养人椎间盘细胞。用白细胞介素-1（IL-1）处理，或用核因子-kappaB（NF-kappaB）活性抑制剂姜黄素处理后，通过逆转录聚合酶链反应（RT-PCR）和 Western blot 检测 Sox9 和胶原 II 的表达，并通过电泳迁移率变动分析（EMSA）检测 NF-kappaB 信号通路的活性。
IL-1 以剂量依赖的方式降低培养的椎间盘细胞中 Sox9 和胶原 II 的 mRNA 水平和蛋白表达（P < 0.05），姜黄素可减弱这种作用。姜黄素单独作用对 Sox9 和胶原 II 的表达没有影响（P > 0.05）。浓度为 0.1ng/ml、1ng/ml 和 10ng/ml 的 IL-1 可剂量依赖性地刺激椎间盘细胞中 NF-kappaB 的活性（P < 0.05），姜黄素可抑制其活性。
我们证明了白细胞介素-1 通过 NF-kappaB 在椎间盘细胞中抑制 Sox9 和胶原 II 的以前未知的功能。这种抑制可以通过姜黄素减弱，姜黄素是一种有效的 NF-kappaB 活性抑制剂。
