Role of PTH1R Signaling in Bone Remodeling During Tooth Eruption

Objectives: Bone remodeling is one of the fundamental requirements for tooth eruption. It is characterized by coupling between osteogenesis and resorption. PTH/PTHrP receptor (PTH1R) signaling plays critical role in craniofacial development and tooth eruption. The underlying mechanism by which PTH1R in mandibular mesenchymal progenitor cells in bone remodeling during tooth eruption is not well-understood.
Methods: We crossed Prx1Cre mice with Cre-dependent ROSA26tdTomato reporter mice to characterize the Prx1⁺ cell population during tooth eruption. We then generated mice with conditional deletion of PTH1R under the control of the Prx1 promoter (Prx1Cre;PTH1R^fl/fl). Micro-CT, histology and qRT-PCR were performed to investigate the effects of PTH1R signaling deficiency during tooth eruption. Mandibular mesenchymal progenitor cells were cultured to examine the effect of PTH1R ablation during osteogenesis in vitro.
Results: We observed high expression of red fluorescence protein of Tomato, representing Prx1⁺ progenitor cells in alveolar bone tissue under molars as well as surrounding the incisors. Ablation of PTH1R by Prx1Cre resulted in arrested eruption of molars and incisors compared to control littermates at P10 and 3-week-old. The phenotype was sustained in a prolonged observation to 6-month-old. Micro-CT analysis revealed that mutant mice had significantly reduced alveolar bone volume, whereas enamel and dentin volume remained unchanged. Mutant mice had statistically lower expression of Runx2, Osx and Col1α1 in alveolar bone at protein and transcript levels compared to control littermates. TRAP and CathepsinK staining suggested PTH1R-dificient mice had comparable osteoclast numbers to controls. Delete PTH1R in mandibular mesenchymal progenitor cells resulted in significantly reduced osteogenesis in vitro.
Conclusions: Conditional deletion of PTH1R in Prx1⁺ mesenchymal progenitor cells leads to molar and incisor eruption failure, which could be partially due to significantly reduced alveolar bone formation, indicating the essential role of PTH1R signaling in mandibular osteogenesis during tooth eruption.