TNF-α induces apoptosis of human nucleus pulposus cells via activating the TRIM14/NF-κB signalling pathway

Cervical spondylosis is a degenerative disease commonly found in older adults and characterized by progressive osteophyte formation and disc collapse. Apoptosis in nucleus pulposus (NP) cells which induced by TNF-alpha has been widely known to associate with the disc degeneration. However, the exactly underlying molecular mechanism was still unclear. The aim of our study was to investigate whether TRIM14/NF-kappa B signalling pathway is associated with the apoptosis of human NP cells (HNPC) induced by TNF-alpha. Our data demonstrated that TNF-alpha treatment obviously decreased the cell viability, induced apoptosis and increased TRIM14 expression and NF-kappa Bp65 activity in HNPC in a dose-dependent manner. Down-regulation of TRIM14 or NF-kappa B inhibitor PDTC treatment significantly inhibited cell apoptosis, Bax/Bcl-2 ratio and NF-kappa Bp65 activation induced by TNF-alpha in HNPC. Meanwhile, up-regulation of TRIM14 obviously increased cell apoptosis, Bax/Bcl-2 ratio and NF-kappa Bp65 activation in HNPC. Then, we found that the protein PPM1A was identified as a binding partner of TRIM14 and ubiquitinated by TRIM14. These findings provide insights into the function of TRIM14 and NF-kappa B signalling and might, therefore, represent a novel therapeutic target for treatment of cervical spondylosis.