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

Objectives Apoptosis 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 methods Rat NP cells were treated with interleukin ( IL)-1β or tumour necrosis factor alpha ( TNF-α), and knockdown of caveolin-1 and β-catenin was achieved using specific si RNAs. Then, apoptotic level of rat NP cells and expression and activation of caveolin-1/β-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. Results IL-1β and TNF-α induced apoptosis, upregulated caveolin-1 expression and activated Wnt/β-catenin signalling in rat NP cells, while the induction effect of cytokines was reversed by caveolin-1 si RNA and β-catenin si RNA. Promotion of rat NP cell apoptosis and nuclear translocation of β-catenin induced by caveolin-1 overexpression were abolished by β-catenin si RNA. Furthermore, pretreatment with a p38 MAPK inhibitor or dominant negative-p38, blocked cytokine-dependent induction of caveolin-1/β-catenin expression and activity. Conclusions The results revealed the role of p38/caveolin-1/β-catenin in inflammatory cytokine-induced apoptosis in rat NP cells. Thus, controlling p38/caveolin-1/β-catenin activity seemed to regulate IL-1β- and TNF-α-induced apoptosis in the NP during intervertebral disc degeneration. [ABSTRACT FROM AUTHOR]