Matrix Stiffness Enhances Odontogenic Differentiation of DPSCs through Membrane Curvature Protein Baiap2‐Modulated Exosome Release

Altered extracellular biomechanical forces are increasingly implicated in a wide range of pathologies. However, the specific role of extracellular matrix stiffness in the pathogenesis of dental caries remains unclear. Although exosomes have been shown to regulate cell fate, it is still poorly understood how their biological journeys from biogenesis to secretion are affected by matrix stiffness. Here we find that matrix stiffness can enhance exosome release, thereby promoting odontogenic differentiation of dental pulp stem cells (DPSCs). Mechanistically, matrix stiffness promotes exosome release by modulating membrane curvature through Baiap2, which is tightly regulated by the stiffness-activated PI3K-AKT signaling pathway. Moreover, the release of exosomes was found to depend on mechanosensitive motor protein kinesin-1 and its regulation of vesicular transport. Taken together, our results demonstrate that matrix stiffness plays an essential role in odontogenic differentiation of DPSCs by modulating exosome release. Our findings prove that the mechanosensitive process may play an underappreciated role in regulating exosome secretion and odontogenic differentiation in deep caries.