Mechanical Loading Induces NRF2 Nuclear Translocation to Epigenetically Remodel Oxidative Stress Defense in Osteocytes.

ABSTRACT: The mechano-responsiveness of osteocytes is critical for maintaining bone health and associated with a reduced oxidative stress defense, yet the precise molecular mechanisms remain incompletely understood. Here, we address the gap by investigating the epigenetic reprogramming that drives osteocyte responses to mechanical loading. We found overall remodeling of antioxidant response under mechanical loading and identified NRF2, a key transcription factor in oxidative stress response, which plays a vital role in the epigenetic remodeling of osteocytes. The results showed that mechanical loading enhanced NRF2 protein stability, promoted its nuclear translocation, and activated osteocyte-specific transcriptional programs. In contrast, pharmacological stabilization of NRF2 failed to fully replic

SUBMITTER: Guo Y 

PROVIDER: S-EPMC11939503 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature