{"data":{"id":"10.25384/sage.c.4040546.v1","type":"dois","attributes":{"doi":"10.25384/sage.c.4040546.v1","prefix":"10.25384","suffix":"sage.c.4040546.v1","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Y. Zhao","affiliation":[],"nameIdentifiers":[]},{"name":"X. Yuan","affiliation":[],"nameIdentifiers":[]},{"name":"B. Liu","affiliation":[],"nameIdentifiers":[]},{"name":"U.S. Tulu","affiliation":[],"nameIdentifiers":[]},{"name":"J.A. Helms","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Wnt-Responsive Odontoblasts Secrete New Dentin after Superficial Tooth Injury"}],"publisher":"Figshare","container":{},"publicationYear":2018,"subjects":[{"subject":"110599 Dentistry not elsewhere classified","subjectScheme":"FOR"},{"subject":"FOS: Clinical medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"91299 Materials Engineering not elsewhere classified","subjectScheme":"FOR"},{"subject":"FOS: Materials engineering","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"}],"contributors":[],"dates":[{"date":"2018-03-23","dateType":"Created"},{"date":"2018-03-23","dateType":"Updated"},{"date":"2018","dateType":"Issued"}],"language":null,"types":{"ris":"GEN","bibtex":"misc","citeproc":"article","schemaOrg":"Collection","resourceType":"Collection","resourceTypeGeneral":"Collection"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.1177/0022034518763151","relatedIdentifierType":"DOI"},{"relationType":"IsIdenticalTo","relatedIdentifier":"10.25384/sage.c.4040546","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":[],"formats":[],"version":null,"rightsList":[{"rights":"CC BY 4.0","rightsUri":"https://creativecommons.org/licenses/by/4.0"}],"descriptions":[{"description":"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 \u003ci\u003eAxin2\u003csup\u003eCreERT2/+\u003c/sup\u003e\u003c/i\u003e; R26R\u003csup\u003e\u003ci\u003emTmG/+\u003c/i\u003e\u003c/sup\u003e 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.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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