Abstract

Human dental pulp stem cells (hDPSCs) hold great promise for dental tissue regeneration, yet the molecular mechanisms underlying their odontogenic differentiation remain unclear. This study investigates the role of nucleoside diphosphate kinase 3 (NME3) in regulating hDPSC differentiation. NME3 was found to be specifically expressed in odontoblasts of rat tooth germs and positively associated with odontogenic markers (DSPP, DMP1, and RUNX2) in hDPSCs. Functional assays revealed that NME3 promotes odontogenic differentiation, while its knockdown suppresses mineralization and marker expression. Mass spectrometry identified N -α-acetyltransferase 10 (NAA10) as a potential NME3-interacting protein, with both showing colocalization in hDPSCs and developing odontoblasts. Mechanistically, NAA10 knockdown rescued the differentiation deficits caused by NME3 silencing, and NAA10 overexpression attenuated the effects of NME3. Moreover, NME3 appears to facilitate the nuclear translocation of RUNX2, a key transcription factor in odontogenesis. These findings suggest that NME3 may regulate hDPSC odontogenic differentiation through interaction with NAA10 and modulation of RUNX2 localization, offering new insights into the molecular control of dental tissue regeneration. Graphical NME3 promotes odontogenic differentiation of hDPSCs, at least in part, through interaction with NAA10 and modulation of RUNX2 nuclear localization. Enhanced nuclear localization of RUNX2 is associated with increased expression of odontogenic markers, including DSPP, DMP1, and ALP. These findings suggest that the NME3-NAA10-RUNX2 axis is involved in regulating odontogenic differentiation.