Effects of Nuclear Factor Kappa B Signaling Pathway in Human Intervertebral Disc Degeneration. Issue 4 (15th February 2015)

• Record Type: Journal Article
• Authors: Zhongyi, Sun; Sai, Zhao; Chao, Liu; Jiwei, Tian
• Is Part Of: Spine. Volume 40:Issue 4(2015)
• Publication Date: 2015-02-15
• Subjects: Spine -- Abnormalities -- Periodicals; Spine -- Diseases -- Periodicals; Spine -- Surgery -- Periodicals; 616.73005
• DOI: 10.1097/BRS.0000000000000733
• Languages: English
• ISSNs: 0362-2436

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Study Design.</title> <p>IL-1β (interleukin-1β) can activate human nucleus pulposus cells with or without nuclear factor kappa B (NF-κB) inhibition. We undertook a descriptive and mechanistic investigation of catabolic effects of NF-κB signaling pathway in intervertebral disc degenerative changes.</p> </sec> <sec> <title>Objective.</title> <p>To clarify the mediatory role of NF-κB signaling pathway in human intervertebral disc degeneration (IDD).</p> </sec> <sec> <title>Summary of Background Data.</title> <p>IDD is a major cause of lower back pain, but the molecular mechanism behind this process is poorly understood. NF-κB is a family of transcription factors that play a central role in mediating cellular response to damage, stress, and inflammation. Growing evidence implicates chronic activation of NF-κB in many degenerative diseases, but its role in IDD has not been adequately explored.</p> </sec> <sec> <title>Methods.</title> <p>Human nucleus pulposus cells in monolayer culture were exposed to IL-1β, which increases matrix-degrading enzyme activity in the nucleus pulposus, with or without NF-κB inhibition by BAY11-7082; ribonucleic acid was isolated for real-time polymerase chain reaction analysis of gene expression, Western blot analysis was performed to detect the changes of protein expression.</p> </sec> <sec> <title>Results.</title> <p>NF-κB specific inhibitor BAY11-7082 significantly inhibited IL-1β–induced NF-κB activation. IL-1β–dependent gene upregulation of matrix metalloproteinase (MMP)-3, MMP-9, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5 was significantly reduced by NF-κB inhibition. The decreased gene expression of aggrecan and type II collagen, induced by IL-1β was also reversed by BAY11-7082. NF-κB inhibition reversed the IL-1β–induced changes of protein expression of MMP-3, MMP-9, MMP-13, ADAMTS-4, ADAMTS-5, aggrecan, and type II collagen.</p> </sec> <sec> <title>Conclusion.</title> <p>These findings demonstrate that the NF-κB signaling pathway is a key mediator of IDD and represents a therapeutic target for mitigating disc degenerative diseases.</p> <p> <bold>Level of Evidence:</bold> N/A</p> </sec> </abstract>