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• W2283315521 abstract "Background Intervertebral disk degeneration (IDD) has a greater than 90% lifetime incidence and is one of the leading causes of chronic back pain in the United States. Despite the high societal cost of IDD, there is limited understanding of the biological effects of mechanical overloading on further degeneration. The transcription factor NF-κB (nuclear factor κB) has been implicated as a key mediator of disk cell response to inflammatory and mechanical stresses and represents a potential control point. Objective The study objective was to measure the effect of NF-κB signaling pathway inhibition on annulus fibrosus (AF) cell matrix synthesis and gene expression under conditions of combined inflammatory and mechanical stimulation. Methods Annulus fibrosus cells were harvested from rabbit intervertebral disks and grown in vitro on flexible plates. The cells were exposed to inflammatory and mechanical stimulation for 24 hours with and without NF-κB inhibition. Nuclear translocation of NF-κB was measured via immunofluorescent staining. Intervertebral disk cell homeostasis was assessed via inflammatory, anabolic, and catabolic gene expression and via matrix synthetic ability. Results NF-κB nuclear translocation in response to interleukin-1 beta (IL-1β) was reversed with exposure to NF-κB inhibition. NF-κB inhibition decreased matrix metalloproteinase-3, inducible nitric oxide synthase, and cyclooxygenase-2 gene expression and prostaglandin E2 production response to combined inflammatory and mechanical stimulation. Proteoglycan and collagen synthesis were decreased by combined stimulation, but this effect was not reversed by NF-κB inhibition. Limitations In vitro modeling of conditions within the disk may not fully reflect the response that AF cells have in native matrix. Conclusions NF-κB signaling mediates catabolic and inflammatory responses to inflammatory and mechanical stimulation but does not mediate the decrease in matrix synthesis under combined harmful stimulation. Identification of key control points in the cellular responses to inflammatory and mechanical stimuli will facilitate rational design of exercise-based therapies and facilitate synergistic treatments of novel biochemical treatments with rehabilitation regimens." @default.
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• W2283315521 date "2016-05-01" @default.
• W2283315521 modified "2023-09-28" @default.
• W2283315521 title "NF-κB Signaling Pathway in Controlling Intervertebral Disk Cell Response to Inflammatory and Mechanical Stressors" @default.
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• W2283315521 doi "https://doi.org/10.2522/ptj.20150045" @default.
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