Nutrient deprivation induces apoptosis of nucleus pulposus cells via activation of the BNIP3/AIF signalling pathway

Nutrient deprivation (ND)-induced nucleus pulposus (NP) cell death serves an important role in intervertebral disc degeneration disease. However, the underlying mechanisms have yet to be thoroughly elucidated. The present study created a cell culture model under ND conditions to investigate the roles of the nutrient-sensitive protein B-cell lymphoma 2/adenovirus E1B 19 kDa-interacting protein (BNIP3) and the mitochondrial pro-death protein apoptosis-inducing factor (AIF) in the death pathway of NP cells. The present study demonstrated that cells subjected to ND for up to 72 h exhibited a time-dependent increase in cell death and decrease in mitochondrial membrane potential (Δψm), as compared with cells cultured under normal conditions. The results of western blotting demonstrated that BNIP3 expression was significantly upregulated in NP cells subjected to ND for 24 h, which coincided with AIF translocation to the cell nucleus and alterations in cell viability and Δψm. Furthermore, BNIP3 overexpression increased ND-induced NP cell death, whereas knockdown of BNIP3 or AIF abolished ND-induced NP cell death. In addition, BNIP3 overexpression increased AIF expression and BNIP3 knockdown decreased AIF expression in NP cells subjected to ND. In conclusion, ND induced NP cell death partially via activation of the BNIP3/AIF signalling pathway. These findings provide novel insights into the potential mechanisms underlying ND-induced death of NP cells during disc degeneration.