Parathyroid hormone-related peptide (1-34) promotes tooth eruption and inhibits osteogenesis of dental follicle cells during tooth development

Dental follicle cells (DFCs) activate and recruit osteoclasts for tooth development and tooth eruption, whereas DFCs themselves differentiate into osteoblasts to form alveolar bone surrounding tooth roots through the interaction with Hertwig's epithelial root sheath (HERS). Also during tooth development, parathyroid hormone-related peptide (PTHrP) is expressed surrounding the tooth germ. Thus, we aimed to investigate the effect of PTHrP (1-34) on bone resorption and osteogenesis of DFCs in vitro and in vivo. In vitro studies demonstrated that DFCs cocultured with HERS cells expressed higher levels of BSP and OPN than the DFCs control group, whereas cocultured DFCs treated with PTHrP (1-34) had lower expressions of ALP, RUNX2, BSP, and OPN than the cocultured DFCs control group. Moreover, we found PTHrP (1-34) inhibited osteogenesis of cocultured DFCs by inactivating the Wnt/β-catenin pathway. PTHrP (1-34) also increased the expression of RANKL/OPG ratio in DFCs. Consistently, in vivo study found that PTHrP (1-34) accelerated tooth eruption and inhibited alveolar bone formation. Therefore, these results suggest that PTHrP (1-34) accelerates tooth eruption and inhibits osteogenesis of DFCs by inactivating Wnt/β-catenin pathway.