title: Resveratrol attenuated TNF-α-induced MMP-3 expression in human nucleus pulposus cells by activating autophagy via AMPK/SIRT1 signaling pathway.
abstract: Resveratrol (RSV) is known to play a role of anti-TNF-α in a number of cell types. However, whether RSV modulates the effects of TNF-α on human nucleus pulposus (NP) cells is unknown. The purpose of this study is to investigate whether RSV regulates TNF-α-induced matrix metalloproteinase-3 (MMP-3) expression. Via quantitative real-time polymerase chain reaction (qRT-PCR) analysis, we found that MMP-3 expression induced by TNF-α was inhibited by RSV treatment. Depending on Western blot and qRT-PCR assay, we found that RSV induced autophagy in human NP cells, whereas inhibition of autophagy remarkably abolished the restraining role of RSV in the TNF-α-mediated up-regulation of MMP-3. Furthermore, RSV increased SIRT1 expression and SIRT1 knockdown significantly suppressed RSV-induced autophagy in NP cells. RSV also activated AMP-activated protein kinase (AMPK), while inhibition of AMPK notably abolished RSV-induced SIRT1 expression. Our data showed that RSV attenuated TNF-α-induced MMP-3 expression in human NP cells by activating autophagy via AMPK/SIRT1 signaling pathway. This new finding suggested that RSV might act as a novel preventive and therapeutic role in intervertebral disc degeneration.
authors.affiliation: Spine Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China.
authors.forename: Xiao-Hu
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Spine Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Spine Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Hong
authors.affiliation: Spine Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China.
authors.forename: Yun-Tao
authors.initials: YT
authors.lastname: Wang
authors.affiliation: Spine Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Spine Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China.
authors.forename: Jun-Ping
authors.initials: JP
authors.lastname: Bao
authors.affiliation: Spine Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China.
authors.forename: Xin-Hui
authors.initials: XH
authors.lastname: Xie
authors.affiliation: Spine Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Spine Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China wuxiaotao@medmail.com.cn.
authors.forename: Xiao-Tao
authors.initials: XT
authors.lastname: Wu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D002478:Cells, Cultured; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D000070614:Nucleus Pulposus / Q000187:drug effects / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D013267:Stilbenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D055372:AMP-Activated Protein Kinases; D019278:Matrix Metalloproteinase 3; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol
keywords: AMPK; MMP-3; Resveratrol; SIRT1; TNF-α; autophagy; nucleus pulposus cell