Kdm6b/Pdk1 Glycolytic Pathway-Driven Zeb2 Lactylation Promotes Cementogenesis

This study investigates the role of KDM6B-mediated glycolytic reprogramming in cementum regeneration, addressing the unclear mechanisms linking epigenetic-metabolic crosstalk to cementoblast mineralization. Cementoblasts (OCCM-30), male C57BL/6 mice (3 weeks to 6 months), and BALB/c-nu nude mice were used. Protocols were approved by the Ethics Committee of University. Methods included RNA-seq, ChIP-qPCR, Seahorse assays, lactylation proteomics, and subcutaneous mineralization models. Statistical significance was assessed via t-tests and ANOVA (P < 0.05). KDM6B promoted cementoblast mineralization by enhancing glycolysis via Pdk1 activation, increasing lactate production. Lactate-driven ZEB2 lactylation (K485 site) stabilized its function, accelerating mineralized nodule formation. In vivo, lactate supplementation rescued impaired cementogenesis caused by KDM6B inhibition. The KDM6B/Pdk1/ZEB2 lactylation axis is critical for cementum regeneration, offering novel therapeutic targets for periodontal and bone regeneration. This study bridges epigenetic regulation, glycolysis, and post-translational modification in mineralization biology.