目的: Nucleus pulposus cells(NPCs) reside in a hypoxic environment in vivo, while the mechanisms of how NPCs maintain survival under hypoxia are not clear. Apoptosis is an important physiological response to hypoxia and implicated in the survival regulation in most types of cells. This study was designed to investigate the role of apoptosis in the survival of NPCs under hypoxia.

方法: In this study, we firstly examined the apoptosis, caspase 3 activity and apoptosis-associated markers in rat NPCs through TNF-α induced cell apoptosis models under normoxia or hypoxia. Then we determined the change of mitochondrial function and the activation of cAMP response element-binding protein (CREB) signaling in these cells.

结果: Our results indicated that hypoxia facilitates rat NPCs survival and up-regulates CREB phosphorylation, ameliorates cell apoptosis through restricting the production of mitochondrial superoxide and reactive oxygen species (ROS), whereas maintaining the certain level of mitochondrial membrane potential (MMP) and Complex IV activity in these cells.

结论: The present study confirmed the up-regulated CREB phosphorylation, along with the ameliorated cell apoptosis induction and mitochondrial dysfunction in the hypoxia-treated rat NPCs, implying the key role of CREB signaling in the intrinsic (mitochondrial) apoptotic pathways. We believed that understanding the response of NPCs to hypoxia and its role in cell survival had important clinical significance in the prevention and treatment of degenerative discogenic diseases.