Oxidative stress activates YAP/TEAD1/NCOA4 axis to promote ferroptosis of endplate chondrocytes and aggravate intervertebral disc degeneration.

ABSTRACT:

Background

Intervertebral disc degeneration (IDD) is a major cause of low back pain, with cartilaginous endplate (CEP) degeneration playing a critical role. While Yes-associated protein (YAP) and its involvement in CEP degeneration and ferroptosis remain unclear. This study aimed to investigate the regulatory role of YAP in CEP ferroptosis and its underlying mechanisms.

Methods

YAP expression was analyzed in human CEP tissues and mouse LSI models. CEP cells were treated with Verteporfin or YAP-siRNA. Ferroptosis was assessed by measuring iron levels, lipid peroxidation, GSH content, and viability assays. Molecular mechanisms were elucidated using CUT&RUN-qPCR, dual-LUC, and immunofluorescence colocalization. Verteporfin (VP) therapeutic efficacy was evaluated in LSI mice.

SUBMITTER: Wang H 

PROVIDER: S-EPMC12274860 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature