Impact of NF-κB pathway on the intervertebral disc inflammation and degeneration induced by over-mechanical stretching stress

• Published in: Journal of inflammation (London, England) Vol. 18; no. 1; p. 6
• Main Authors: Xu, Hui, Qi, Guobao, Li, Kunpeng, Yang, Keshi, Luo, Dawei, Cai, Zhongxu
• Format: Journal Article
• Language: English
• Published: England BioMed Central 02.02.2021; BMC
• Subjects: Aggrecan; Antibodies; Apoptosis; Back pain; Cell culture; Cell viability; Collagen (type II); Collagenase 3; Degeneration; Degenerative disc disease; Extracellular matrix; Flow cytometry; IL-1β; Inflammation; Intervertebral disc; Intervertebral discs; Low back pain; Matrix metalloproteinase; Mechanical stretching stress; Metalloproteinase; NF-κB; NF-κB protein; Nucleus pulposus; Signal transduction; siRNA; Stromelysin 1; Transfection; Tumor necrosis factor-TNF; Tumor necrosis factor-α; United States > US; China; NF-κB; Degeneration; Inflammation; Intervertebral disc; Mechanical stretching stress
• ISSN: 1476-9255; 1476-9255
• DOI: 10.1186/s12950-021-00273-9

Intervertebral disk degeneration (IVDD) contributes to low back pain. Increased cell apoptosis and inflammation, decreased extracellular matrix are associated with IVDD. Nuclear factor-kappa B (NF-κB) signaling pathway and inflammatory cytokines are implicated in the pathophysiology of IVDD. In present study, we established a mechanical stretching stress-stimulated nucleus pulposus (NP) cell model. We knocked down NF-κB p65 by siRNA transfection to inhibit NF-κB and evaluated the effects of NF-κB inhibition on intervertebral disk degeneration. We applied the mechanical stretching stress on NP cells and inhibited NF-κB by siRNA, then evaluated the expression of inflammatory cytokines, matrix metalloproteinase (MMP), aggrecan, collagen II, and monitored viability and apoptosis of NP cells. Mechanical stretching stress induced the expression of TNF-α, IL-1β, NF-κB, MMP-3 and MMP-13, while inhibited the production of aggrecan and collagen II in NP cells. Mechanical stretching stress decreased the cell viability and induced apoptosis in NP cells. Inhibition of NF-κB by siRNA suppressed the production of TNF-α, IL-1β, NF-κB, MMP-3 and MMP-13, while upregulated the expression of aggrecan and collagen II in NP cells. Inhibition of NF-κB by knocking down p65 suppressed over-mechanical stretching stress-induced cell apoptosis and promoted viability in NP cell. Inhibition of NF-κB suppressed inflammation and degeneration of NP cells in IVDD.