A Three-dimensional Analysis of Primary Failure of Eruption in Humans and Mice.

Abstract

OBJECTIVES\nPrimary 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-micro CT analyses.\n\n\nSETTING AND SAMPLE POPULATION\nTwo individual 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).\n\n\nMATERIALS AND METHODS\nImages from human PFE subjects were acquired by CBCT. All groups of mouse samples were studied at postnatal day 14, 25, 91 and 182 after a tamoxifen pulse at P3, and superimposition of 3D-microCT images among three groups was rendered.\n\n\nRESULTS\nMouse 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.\n\n\nCONCLUSIONS\nMouse PFE molars erupt at a much slower rate compared to normal molars, associated with shortened and dilacerated roots and defective interradicular bones.