Title: Regulation of Tertiary Dentin Formation in Odontoblast-specific EphrinB1 Knockout Mice
Lucy Hovanisyan (Presenter)
New York University
Shoshana Yakar, New York University
Objectives: Ephrins are membrane-spanning ligands that bind to and activate Eph receptors, a subfamily of receptor tyrosine kinases. The interaction between ephrinB1 and EphB2 at the cell membrane initiates bidirectional signaling fundamental for tooth repair. EphrinB1-EphB2 interaction stimulates odontoblast proliferation and differentiation from dental pulp cells during the early stages of tooth injury, as well as promotes tertiary dentin formation. During tooth development, ephrinB1 and EphB2 are expressed in pre-odontoblasts and odontoblasts, and ephrinB1 alone is expressed in odontoblasts until the completion of tooth eruption. Studies in mouse models have shown that ephrinB1 is upregulated in odontoblasts 2 weeks following tooth injury without pulp exposure, while EphB2 is expressed only in the center of pulp niches. Our goal was to investigate the role of ephrinB1 in regulating tertiary dentin formation following tooth injury.
Methods: Tooth injury was induced in the right mandibular first molar. Following anesthesia, the occlusal surfaces of the right mandibular first molars were injured halfway into the dentin layer using a No. 2 round bur drill, air-dried, and sealed with Cavit (Premier). Tertiary dentin was analyzed 4 weeks following injury using micro computed tomography (μCT) at 7.5 micron resolution. We used three groups of mice; controls (wild type mice), pre-odontoblast-specific ephrinB1 null mice (OC/ephrinB1), and mature odontoblast-specific ephrinB1 null mice (DMP/ephrinB1).
Results: We found ~20% decreased tertiary dentin volume in mice with pre-odontoblast-specific ephrinB1 gene knockout as compared to controls, while tertiary dentin volume in mature odontoblast-specific ephrinB1 null mice did not differ from that of controls. Interestingly, we found that mice with pre-odontoblast-specific ephrinB1 gene deletion showed ~8% increase in enamel mineral density.
Conclusions: Our data suggest that ephrinB1 plays important roles in tooth recovery following injury. Specifically, expression of ephrinB1 is required in pre-odontoblasts to allow tertiary dentin formation.