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J Dent Res. 2018 Aug;97(9):1047-1054. doi: 10.1177/0022034518763151. Epub 2018 Mar 22.

Wnt-Responsive Odontoblasts Secrete New Dentin after Superficial Tooth Injury.

Author information

1
1 Department of Oral Basic Science, School of Dentistry, Lanzhou University, Lanzhou, China.
2
2 Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA.
3
3 Ankasa Regenerative Therapeutics, Inc., South San Francisco, CA, USA.

Abstract

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 HIF1α; and the rate of mineralization was significantly increased. A tamoxifen-inducible Axin2CreERT2/+; 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.

KEYWORDS:

Wnt3A protein; cell death; dental pulp; dentinogenesis; molar; regeneration

PMID:
29566345
PMCID:
PMC6055255
DOI:
10.1177/0022034518763151
[Indexed for MEDLINE]
Free PMC Article

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