Oxygen-Sensing Nox4 Generates Genotoxic ROS to Induce Premature Senescence of Nucleus Pulposus Cells through MAPK and NF-κB Pathways.

ABSTRACT: Senescence is a crucial driver of intervertebral disc degeneration (IDD). Disc cells are exposed to high oxygen tension due to neovascularization in degenerative discs. However, the effect of oxygen tension on disc cell senescence was unknown. Herein, rat nucleus pulposus (NP) cells were cultured under 20% O₂ or 1% O₂. Consequently, ROS induced by 20% O₂ caused DNA damage and then activated p53-p21-Rb and p16-Rb pathways via ERK signaling to induce NP cell senescence. It also induced catabolic and proinflammatory phenotype of NP cells via MAPK and NF-κB pathways. Furthermore, 20% O₂ was found to upregulate Nox4 in NP cells. Small interfering RNA against Nox4 reduced ROS production induced by 20% O₂ and consequently suppressed pr

SUBMITTER: Feng C 

PROVIDER: S-EPMC5632907 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature