A three‐dimensional analysis of primary failure of eruption in humans and mice

• Published in: Oral diseases Vol. 26; no. 2; pp. 391 - 400
• Main Authors: Tokavanich, Nicha, Gupta, Aditi, Nagata, Mizuki, Takahashi, Akira, Matsushita, Yuki, Yatabe, Marilia, Ruellas, Antonio, Cevidanes, Lucia, Maki, Koutaro, Yamaguchi, Tetsutaro, Ono, Noriaki, Ono, Wanida
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01.03.2020
• Subjects: Animals; Cell differentiation; Child, Preschool; Computed tomography; Dental roots; Dental Sac - abnormalities; Dentistry; Dimensional analysis; Female; Genetic disorders; Humans; Imaging, Three-Dimensional; Infant; Loss of Function Mutation; Male; Mice; Molar - abnormalities; Molars; Parathyroid; Parathyroid hormone; Parathyroid hormone-related protein; parathyroid hormone‐related peptide receptor type i; primary failure of eruption; receptor mutations; Receptor, Parathyroid Hormone, Type 1 - genetics; Statistical analysis; Tamoxifen; Teeth; Tooth Diseases - genetics; tooth eruption; Tooth Eruption - genetics; tooth root formation; Tooth, Deciduous - abnormalities; parathyroid hormone; parathyroid hormone-related peptide receptor type i; tooth root formation; tooth eruption; receptor mutations; primary failure of eruption
• ISSN: 1354-523X; 1601-0825
• DOI: 10.1111/odi.13249

Objectives Primary failure of eruption (PFE) is a genetic disorder exhibiting the cessation of tooth eruption. Loss‐of‐function mutations in parathyroid hormone (PTH)/parathyroid hormone‐related peptide (PTHrP) receptor (PTH/PTHrP receptor, PPR) were reported as the underlying cause of this disorder in humans. We showed in a PFE mouse model that PTHrP‐PPR signaling is responsible for normal dental follicle cell differentiation and tooth eruption. However, the mechanism underlying the eruption defect in PFE remains undefined. In this descriptive study, we aim to chronologically observe tooth eruption and root formation of mouse PFE molars through 3D microCT analyses. Setting and Sample Population Two individuals with PFE were recruited at Showa University. A mouse PFE model was generated by deleting PPR specifically in PTHrP‐expressing dental follicle and divided into three groups, PPRfl/fl;R26RtdTomato/+(Control), PTHrP‐creER;PPRfl/+;R26RtdTomato/+(cHet), and PTHrP‐creER;PRRfl/fl;R26RtdTomato/+(cKO). Materials and Methods Images from human PFE subjects were acquired by CBCT. All groups of mouse samples were studied at postnatal days 14, 25, 91, and 182 after a tamoxifen pulse at P3, and superimposition of 3D microCT images among three groups was rendered. Results Mouse and human PFE molars exhibited a similar presentation in the 3D CT analyses. The quantitative analysis in mice demonstrated a statistically significant decrease in the eruption height of cKO first and second molars compared to other groups after postnatal day 25. Additionally, cKO molars demonstrated significantly shortened roots with dilacerations associated with the reduced interradicular bone height. Conclusions Mouse PFE molars erupt at a much slower rate compared to normal molars, associated with shortened and dilacerated roots and defective interradicular bones.