Huang Yao, Chen Jian, Jiang Tao, Zhou Zheng, Lv Bin, Yin Guoyong, Fan Jin
Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, P.R. China.
Oncotarget. 2017 Jul 18;8(29):47665-47674. doi: 10.18632/oncotarget.17509.
This study investigated the inhibitory effect of gallic acid (GA) on the release of A Disintegrin and Metalloproteinase with Thrombospondin motifs 4 (ADAMTS4) through the regulation of the NF-κB signaling pathway, which is closely related to the matrix metalloproteinases in nucleus pulposus cells. Different concentrations of GA were added to TNF-α-induced human nucleus pulposus cells (hNPCs) and intervertebral disc degeneration rat model. ADAMTS-4 expression increased both in the TNF-α-induced nucleus pulposus cells and intervertebral disc degeneration rat model. By contrast, the release of ADAMTS-4 was reduced, and the TNF-α-induced apoptosis of nucleus pulposus cells was significantly inhibited after addition of GA at different concentrations. Further study found that the levels of phosphorylated p65 (p-p65) was increased and the classical NF-κB signal pathway was activated after the nucleus pulposus cells were stimulated by TNF-α. Meanwhile, GA suppressed the p65 phosphorylation and inceased p65 deacetylation levels. As a consequence, GA can decrease the expression of ADAMTS-4 in nucleus pulposus cells by regulating the phosphorylation and acetylation of p65 in NF-κB signaling pathways.
本研究通过调节与髓核细胞中基质金属蛋白酶密切相关的核因子κB（NF-κB）信号通路，探讨了没食子酸（GA）对含血小板反应蛋白基序的解聚素样金属蛋白酶4（ADAMTS4）释放的抑制作用。将不同浓度的GA添加到肿瘤坏死因子-α（TNF-α）诱导的人髓核细胞（hNPCs）和椎间盘退变大鼠模型中。在TNF-α诱导的髓核细胞和椎间盘退变大鼠模型中，ADAMTS-4表达均增加。相比之下，添加不同浓度的GA后，ADAMTS-4的释放减少，且TNF-α诱导的髓核细胞凋亡受到显著抑制。进一步研究发现，TNF-α刺激髓核细胞后，磷酸化p65（p-p65）水平升高，经典NF-κB信号通路被激活。同时，GA抑制p65磷酸化并提高p65去乙酰化水平。因此，GA可通过调节NF-κB信号通路中p65的磷酸化和乙酰化来降低髓核细胞中ADAMTS-4的表达。
