Project Details
Projekt
Primary failure of tooth eruption due to heterozygous mutations in the PTH1 receptor gene: Generation and characterization of cell models with clinically relevant mutations and development of therapeutic strategies.
Subject Area
Dentistry, Oral Surgery
Term
from 2021 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 453600987
Dental eruption into the oral cavity requires controlled bone remodeling crucially controlled by osteoblasts, periodontal periligamentary cells and resident mesenchymal stem cells. Non-syndromic primary failure of tooth eruption is caused by heterozygous mutations of the parathormone receptor type 1 (PTH1R), which is expressed in high density by the above mentioned cells. Until now, cell biological characterization was performed only with a few selected mutants showing a decreased or complete loss of receptor functions. However, interactions with the wild type receptor as well as potential cellular effects in the heterozygous context are not yet well understood. By applying Cripsr/Cas9 technology, this proposal aims to develop heterozygous PTH1R mutant cell lines of cells, which are directly involved in the tooth eruption process. Main focus will be the subcellular localization of mutant and wild type PTH1R, the biochemical analysis of PTH-regulated signalling pathways and downstream epigenetic targets as well as recording of potential changes in the cellular proteome, and the cell biological analysis of cell proliferation and differentiation. Based on these data, a concept for restoring disturbed PTH-regulated cellular functions will be developed by direct activation of affected signalling pathways. This will open a chance for pharmacological treatment of the – until now not treatable – primary failure of tooth eruption.
DFG Programme
Research Grants
