Dnmt3a-mediated hypermethylation of FoxO3 promotes redox imbalance during osteoclastogenesis.

ABSTRACT: Redox imbalance contributes to aberrant osteoclastogenesis and osteoporotic bone loss. In this study, we observed lower Forkhead box protein O3 (FoxO3), a transcription factor associated with cellular oxidative stress, enhanced osteoclastogenesis in osteoporosis (OP). Single-cell RNA sequencing (scRNA-seq) analysis on the human femoral head indicated that FoxO3 is widely expressed in macrophages. Furthermore, Lysm-Cre;FoxO3^f/f OVX mice showed increased reactive oxygen species (ROS), enhanced osteoclastogenesis, and more bone loss than normal OVX mice. Mechanistically, we identified FoxO3 promoter methylation as a crucial factor contributing to decreased FoxO3, thereby influencing osteoclastogenesis and OC function. Intriguingly, we observed that Dnmt3a, highly expressed during o

SUBMITTER: Zhang W 

PROVIDER: S-EPMC11962505 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature