Hif-1Α Drives Maxillary Expansion Via Citrate Mitochondrial-Nuclear Crosstalk

This study aims to investigate the molecular mechanisms by which micro-osseous perforations (MOPs) drive maxillary skeletal expansion. It focuses on how citrate accumulation and histone lysine acetylation, mediated by HIF-1α under hypoxia, regulate osteoclast activity and bone remodeling. The goal is to provide a theoretical basis for optimizing MOPs in clinical practice. Gene-edited mice models were used to examine HIF-1α’s role in bone metabolism. Radioactive isotope tracing tracked citrate’s metabolic pathways, while ATAC-Seq analyzed chromatin accessibility and histone acetylation during osteoclast activation. Hypoxia induced by MOPs triggered HIF-1α-dependent TCA cycle blockage, leading to citrate accumulation. Citrate-derived Ac-CoA promoted histone acetylation, enhancing chromatin accessibility for bone resorption genes. ATAC-Seq revealed dynamic epigenetic changes linked to osteoclast activation. MOPs drive bone remodeling via HIF-1α-mediated citrate metabolism and histone acetylation, coupling metabolic and epigenetic regulation. This mechanism highlights citrate’s role in mitochondrial-nuclear communication, offering insights for clinical maxillary expansion strategies.