Ciliary IFT80 regulates dental pulp stem cells differentiation by FGF/FGFR1 and Hh/BMP2 signaling

Primary cilia and intraflagellar transport (IFT) proteins control a wide variety of processes during development and tissue homeostasis. However, their potential roles in the regulation of stem cell differentiation and tooth development remain elusive. Here, we uncovered the critical roles of ciliary IFT80 in cilia formation and differentiation of dental pulp stem cells (DPSCs). IFT80-deficient DPSCs showed reduced fibroblast growth factor receptor 1 (FGFR1) expression, leading to the disruption of FGF2-FGFR1 signaling. We found, during DPSC differentiation, FGF2-FGFR1 signaling induces stress fiber rearrangement to promote cilia elongation, meanwhile stimulates PI3K-AKT signaling to aid Hh/bone morphogenetic protein 2 (BMP2) signaling activation. These signaling pathways and their coupling were disrupted in IFT80-deficient DPSCs, causing impaired differentiation. Our findings revealed a novel mechanism that ciliary protein regulates the odontogenic differentiation of DPSCs through FGF/FGFR1 and Hh/BMP2 signaling.