Title: 3D MicroCT Perspective on Importance of PTHrP-PPR for Tooth Eruption
Aditi Gupta (Presenter)
University of Michigan School of Dentistry
Akira Takahashi, University of Michigan School of dentistry
Antonio Ruellas, Federal University of Rio de Janeiro
Lucia Cevidanes, University of Michigan
Noriaki Ono, University of Michigan
Wanida Ono, University of Michigan School of Dentistry
Objectives: Understanding the pathways that control tooth eruption and root formation is an essential prerequisite for regenerative and clinical dentistry. Dental follicle is indispensable for tooth eruption and is known to include progenitor cells for root formation. The aim of this study is to evaluate the effects of PTHrP-PPR signaling on tooth eruption and root formation; as well as the disease progression at different time points, through 3D MicroCT analysis.
Methods: We have previously reported that parathyroid hormone-related protein (PTHrP) and its receptor (PPR) signaling in osterix-expressing mesenchymal cells affects tooth eruption and root formation. Heterozygous loss-of-function mutations in PPR lead to primary failure of tooth eruption (PFE) in humans. We have successfully established the mouse model of dental follicle-specific loss of PPR (PTHrP-CreERt; PPRf/f). This mouse model mimics human PFE.
We hypothesized that deletion of PPR in the dental follicle will lead to molar under-eruption and shorter roots. For the experiment, Control (WT)/ Heterozygote (cHet) and Knockout (KO) littermate mice were studied at postnatal day 14, day 25, day 91 and day 182. MicroCT images of the samples were taken and segmented with ITK Snap; and labels/markers were created and analyzed with SlicerCMF.
Results: Quantitative analysis revealed that there was a statistically significant difference between the height of eruption and root length of the mandibular first molars between WT/cHet and KO (Fig 1). The difference in height of eruption and root length became pronounced from P14 to P182. In correlation with previous immunochemistry and histological findings, morphological changes were restricted to the root, whereas the crown of the molar was unaffected.
Conclusions: The experiment underscores the importance of PTHrP-PPR signaling in the dental follicle for tooth eruption and root formation and; demonstrates that 3D MicroCT analysis is a powerful tool to study the process of tooth eruption and root formation in rodent samples.