Effects of Nuclear Factor Kappa B Signaling Pathway in Human Intervertebral Disc Degeneration

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Study Design.

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.


To clarify the mediatory role of NF-κB signaling pathway in human intervertebral disc degeneration (IDD).

Summary of Background Data.

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.


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.


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.


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.


Level of Evidence: N/A

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