Inflammatory cytokines induce caveolin-1/-catenin signalling in rat nucleus pulposus cell apoptosis through the p38 MAPK pathway

ObjectivesApoptosis of nucleus pulposus (NP) cells is a major cause of intervertebral disc degeneration. To elucidate relationships between caveolin-1 and cytokine-induced apoptosis, we investigated the role of caveolin-1 in cytokine-induced apoptosis in rat NP cells and the related signalling pathway. Materials and methodsRat NP cells were treated with interleukin (IL)-1 or tumour necrosis factor alpha (TNF-), and knockdown of caveolin-1 and -catenin was achieved using specific siRNAs. Then, apoptotic level of rat NP cells and expression and activation of caveolin-1/-catenin signalling were assessed by flow cytometric analysis, qRT-PCR, western blotting and luciferase assays. The relationship between the mitogen-activated protein kinase (MAPK) pathway and caveolin-1 promoter activity was also determined by luciferase assays. ResultsIL-1 and TNF- induced apoptosis, upregulated caveolin-1 expression and activated Wnt/-catenin signalling in rat NP cells, while the induction effect of cytokines was reversed by caveolin-1 siRNA and -catenin siRNA. Promotion of rat NP cell apoptosis and nuclear translocation of -catenin induced by caveolin-1 overexpression were abolished by -catenin siRNA. Furthermore, pretreatment with a p38 MAPK inhibitor or dominant negative-p38, blocked cytokine-dependent induction of caveolin-1/-catenin expression and activity. ConclusionsThe results revealed the role of p38/caveolin-1/-catenin in inflammatory cytokine-induced apoptosis in rat NP cells. Thus, controlling p38/caveolin-1/-catenin activity seemed to regulate IL-1- and TNF--induced apoptosis in the NP during intervertebral disc degeneration.