CD24+ human dental papilla cells as translational seed cells for dentin-pulp regeneration via BMP2/SIRT1 metabolic axis

Mechanistically, we delineate a BMP2-driven metabolic axis in which elevated BMP signaling sustains SIRT1 expression and promotes mitochondrial metabolism. Inhibition of BMP signaling disrupts this axis, activating WNT signaling, reducing SIRT1 expression, compromising antioxidant and autophagic responses, and consequently diminishing odontogenic capacity. Furthermore, BMP signaling in CD24⁺ hDPCs induces VEGF expression, enhancing endothelial cell recruitment and neovascularization via paracrine effects.

CD24 also acts as a downstream marker of odontogenic BMP signaling, reflecting BMP pathway activation and correlating with odontogenic potential, although it does not directly mediate differentiation. Together, our findings characterize CD24⁺ hDPCs as a regeneration-competent subpopulation that integrates mitochondrial metabolism and signaling crosstalk to enable coordinated dentin and pulp regeneration, representing a translationally relevant cell source for dental tissue engineering.