PIEZO1-GPX4 Axis Mediates Mechanical Stress-Induced Vertebral Growth Plate Dysplasia via Ferroptosis Activation.

ABSTRACT: Current scientific consensus acknowledges mechanical stress, particularly compressive loading, as a critical contributor to the pathogenesis of vertebral growth plate disorders (VGPD), though the precise molecular mechanisms remain incompletely understood. This study establishes PIEZO1 as a mechanosensitive ion channel central to compressive stress responses. These findings demonstrate that PIEZO1 upregulation disrupts GPX4 signaling, thereby amplifying ferroptosis in vertebral growth plate chondrocytes and accelerating pathological ossification. Pharmacological inhibition of PIEZO1 effectively attenuated iron overload, mitigated oxidative stress, and suppressed mechanical stress-induced ferroptosis cascades. Notably, both conditional PIEZO1 knockout models (Col2a1-CreERT; Piezo1^flox/

SUBMITTER: Chen F 

PROVIDER: S-EPMC12533149 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature