Effects of the NF-κB/p53 signaling pathway on intervertebral disc nucleus pulposus degeneration

The incidence of intervertebral disc degeneration (IDD) is increasing, especially among elderly individuals. The present study aimed to investigate the effects of the NF-κB/p53 signaling pathway on IDD and its regulatory effect on associated cytokines. In the present study, human nucleus pulposus cells were isolated from patients with thoracic-lumbar fractures and patients with IDD to observe cellular morphology and detect phosphorylated (p)-p65/p53 expression levels. The locality and expression levels of p65 in interleukin (IL)-1β-stimulated nucleus pulposus cells, with or without the addition of ammonium pyrrolidinedithiocarbamate (PDTC; a NF-κB signaling pathway-specific blocker), were measured. Furthermore, the effects of IL-1β stimulation on the protein and gene expression levels of IDD-related cytokines were determined following p53 knockdown and inhibition of the NF-κB signaling pathway. The results suggested that p-p65 and p53 expression was significantly increased in IDD cells compared with normal nucleus pulposus cells. Moreover, nucleus pulposus cells isolated from patients with IDD contained less cytoplasm compared with normal nucleus pulposus cells, and p65 expression levels were higher in the cytoplasm than the nucleus of IL-1β-stimulated PDTC-treated healthy nucleus pulposus cells. Moreover, the p53 expression levels were significantly decreased following transfection with sip53. PDTC treatment and p53 knockdown significantly decreased matrix metallopeptidase (MMP)-3, MMP-13, metallopeptidases with thrombospondin type 1 motif (ADAMTS)-4 and ADAMTS-5 expression levels, and increased aggrecan and collagen type II expression levels in IL-1β-stimulated cells. The present study indicated that activation of the NF-κB/p53 signaling pathway might be related to the occurrence of IDD; therefore, the NF-κB/p53 signaling pathway may serve as a therapeutic target for IDD.