Gallic acid inhibits the release of ADAMTS4 in nucleus pulposus cells by inhibiting p65 phosphorylation and acetylation of the NF-κB signaling pathway

// Yao Huang 1, * , Jian Chen 1, * , Tao Jiang 1, * , Zheng Zhou 1 , Bin Lv 1 , Guoyong Yin 1 and Jin Fan 1 1 Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, P.R. China * These authors have contributed equally to this work Correspondence to: Guoyong Yin, email: guoyong_yin@sina.com Jin Fan, email: fanjin@njmu.edu.cn Keywords: GA, ADAMTS4, NF-κB, p65, degeneration Received: March 17, 2017      Accepted: March 30, 2017      Published: April 28, 2017 ABSTRACT 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.