Glutamine-αKG axis affects dentin regeneration and regulates osteo/odontogenic differentiation of mesenchymal adult stem cells via IGF2 m6A modification

• The glutamine-αKG axis is upregulated during osteo/odontogenic differentiation of dental pulp stem cells, and αKG supplementation accelerates dentin repair in a mouse incisor clipping model. • GLUD1 knockdown reduces αKG levels, impairing osteo/odontogenic differentiation, while exogenous αKG rescues this effect, highlighting the axis's regulatory role. • Mechanistically, the glutamine-αKG axis influences IGF2 translation via m6A methylation, affecting ECM function and PI3K-Akt signaling, which are critical for differentiation. • These findings suggest that targeting glutamine metabolism could enhance dental pulp stem cell-based regenerative therapies for dentin and bone defects.