| First Author | Zhao Y | Year | 2018 |
| Journal | J Dent Res | Volume | 97 |
| Issue | 9 | Pages | 1047-1054 |
| PubMed ID | 29566345 | Mgi Jnum | J:379988 |
| Mgi Id | MGI:8279065 | Doi | 10.1177/0022034518763151 |
| Citation | Zhao Y, et al. (2018) Wnt-Responsive Odontoblasts Secrete New Dentin after Superficial Tooth Injury. J Dent Res 97(9):1047-1054 |
| abstractText | The objective of our experiments was to identify new therapeutic strategies to stimulate dentin formation in an adult tooth. To address this objective, we evaluated dentin production in 2 acute trauma models: one involving a pulp exposure and the other involving a superficial dentin injury. Molecular, cellular, and histologic analyses revealed that in response to a severe injury, where the pulp is exposed to the oral cavity, cell death is rampant and the repair response initiates from surviving pulp cells and, to a lesser extent, surviving odontoblasts. When an injury is superficial, as in the case of a dentin injury model, then disturbances are largely confined to pulp tissue immediately underneath the damaged dentin tubules. We found that the pulp remained vital and innervated; primary odontoblasts upregulated HIF1alpha; and the rate of mineralization was significantly increased. A tamoxifen-inducible Axin2(CreERT2/+); R26R (mTmG/+) reporter strain was then used to demonstrate that a population of long-lived Wnt-responsive odontoblasts, which secreted dentin throughout the life of the animal, were responsible for depositing new dentin in response to a superficial injury. Amplifying Wnt signaling in the pulp stimulates dentin secretion, and in the dentin injury model, we show that a liposomal formulation of human WNT3A protein passes through dentinal tubules and is capable of upregulating Wnt signaling in the pulp. These data provide strong proof of concept for a therapeutic pulp-capping material to stimulate Wnt signaling in odontoblasts and thus improve the pulp repair response. |