IL-1β promotes ADAMTS enzyme-mediated aggrecan degradation through NF-κB in human intervertebral disc

BACKGROUND: The purpose of this study is to investigate IL-1β regulation of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-4 and ADAMTS-5) expression through nuclear factor kappa B (NF-κB) in human nucleus pulposus (NP) cells. METHODS: qRT-PCR and Western blot were used to measure ADAMTS expression. Transfections and gene silencing were used to determine the role of NF-κB on cytokine-mediated ADAMTS expression and its role in aggrecan degradation. RESULTS: IL-1β increased ADAMTS expression in NP cells. Treatment with NF-κB inhibitors abolished the inductive effect of the cytokines on ADAMTS expression. Silencing of p65 confirmed their role in IL-1β-dependent ADAMTS-4 and ADAMTS-5 expression and aggrecan degradation. CONCLUSIONS: By controlling the activation of NF-κB signaling, IL-1β modulates the expression of ADAMTS in NP cells. To our knowledge, this is the first study that shows the contribution of both ADAMTS-4 and ADAMTS-5 to aggrecan degradation in human NP cells.