Excessive Wnt signaling disrupts periodontium development

YUAN X; WU Y; PELLEGRINI GG; BELLIDO T; HELMS JA

Congreso; American Society for Bone and Mineral Research Annual Meeting; 2017

ASBMR

Teeth are anchored to the jawbones by the periodontium, a tripartite structure consisting of cementum, periodontal ligament (PDL), and alveolar bone. Cementum covers the tooth root and provides an attachment site for the fibrous PDL; the other end of the PDL is tethered to alveolar bone. This arrangement provides a flexible attachment between the tooth to the jawbone, allowing for tooth movement, especially in response to large bite forces1. Our goal was to understand the molecular mechanisms responsible for creating the periodontium.DaβcatOt mice were generated by crossing DMP1-8kb-Cre+/− and Catnblox(ex3)/lox(ex3) mice 2. Wnt1CreR26RLacZ/+ mice were generated by crossing Wnt1Cre+/- and R26R mice 3. Micro-computed tomography (µCT) scans were reconstructed with ScanIP. Tissues were analyzed using histology, enzymatic activity assays and immunohistochemistry for markers of apoptosis, proliferation, and differentiation. Histological and µCT analyses demonstrated that tooth eruption was perturbed in daβcatOt mice. The eruption defect was not due to perturbed osteoclast activity, as monitored by TRAP staining. Rather, daβcatOt teeth lacked a PDL; in its place was a mineralized tissue and excessive amounts of cellular cementum, which fused the tooth to the alveolar bone. The molecular mechanism responsible for this ankylosis phenotype was aberrantly high Wnt signaling in the initial population of cranial neural crest cells that form the periodontium, which increased both cellular cementum and alveolar bone production at the expense of the fibrous PDL. In stem mammals including amphibians, reptiles, and dinosaurs, ankylosis represents the ancestral means by which teeth are anchored to the jawbones 4; in mammals, ankylosis represents a pathological condition. Our data demonstrate that a simple molecular switch, mediated by Wnt signaling, is responsible for creating the periodontium from a single population of cranial neural crest cells, and that aberrantly high Wnt signaling in the progeny of cementoblasts and osteoblasts is sufficient to recreate this stem state in mammals. These data provide clues as to how the periodontium initially forms during odontogenesis, and the influence of Wnt signaling on the formation and maintenance of both mineralized and unmineralized tissues of the dentition.