title: Wnt Acts as a Prosurvival Signal to Enhance Dentin Regeneration.
abstract: Wnt proteins are lipid-modified, short-range signals that control stem cell self-renewal and tissue regeneration. We identified a population of Wnt responsive cells in the pulp cavity, characterized their function, and then created a pulp injury. The repair response was evaluated over time using molecular, cellular, and quantitative assays. We tested how healing was impacted by wound environments in which Wnt signaling was amplified. We found that a Wnt-amplified environment was associated with superior pulp healing. Although cell death was still rampant, the number of cells undergoing apoptosis was significantly reduced. This resulted in significantly better survival of injured pulp cells, and resulted in the formation of more tertiary dentin. We engineered a liposome-reconstituted form of WNT3A then tested whether this biomimetic compound could activate cells in the injured tooth pulp and stimulate dentin regeneration. Pulp cells responded to the elevated Wnt stimulus by differentiating into secretory odontoblasts. Thus, transiently amplifying the body's natural Wnt response resulted in improved pulp vitality. These data have direct clinical implications for treating dental caries, the most prevalent disease affecting mankind.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hunter
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA.|EA 2496, Dental School, University Paris Descartes, Sorbonne Paris Cité, Montrouge, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Bardet
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA.|Department of Periodontology, Service of Odontology, Rothschild Hospital, Assistance Publique-Hôpitaux de Paris, Paris 7, Université Paris Diderot, Unité de Formation et de Recherche (UFR) of Odontology, Paris, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Mouraret
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA.
authors.forename: Gurpreet
authors.initials: G
authors.lastname: Singh
authors.affiliation: EA 2496, Dental School, University Paris Descartes, Sorbonne Paris Cité, Montrouge, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Sadoine
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA.
authors.forename: Girija
authors.initials: G
authors.lastname: Dhamdhere
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA.|Department of Biological Sciences, San Jose State University, San Jose, CA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Smith
authors.affiliation: EA 2496, Dental School, University Paris Descartes, Sorbonne Paris Cité, Montrouge, France.
authors.forename: Xuan Vinh
authors.initials: XV
authors.lastname: Tran
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Joy
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Rooker
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA.|Department of Dental Science for Health Promotion, Division of Cervico-Gnathostomatology Hiroshima, University Graduate School of Biomedical Sciences, Hiroshima, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: BioMediTech, Adult Stem Cell Research, University of Tampere, Tampere, Finland.|Finnish Student Health Service, Tampere, Finland.
authors.forename: Annukka
authors.initials: A
authors.lastname: Vuorinen
authors.affiliation: BioMediTech, Adult Stem Cell Research, University of Tampere, Tampere, Finland.|Science Centre, University of Tampere, Tampere, Finland.
authors.forename: Susanna
authors.initials: S
authors.lastname: Miettinen
authors.affiliation: EA 2496, Dental School, University Paris Descartes, Sorbonne Paris Cité, Montrouge, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Chaussain
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford School of Medicine, Stanford, CA, USA.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Helms
mesh_terms: D000818:Animals; D017209:Apoptosis; D060466:Axin Protein / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D003782:Dental Pulp / Q000378:metabolism / Q000473:pathology; D003804:Dentin / Q000378:metabolism*; D017353:Gene Deletion; D006706:Homeostasis; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D009804:Odontoblasts / Q000378:metabolism; D009805:Odontogenesis; D051381:Rats; D012038:Regeneration / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D013234:Stem Cells / Q000378:metabolism; D060509:Wnt3A Protein / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D060466:Axin Protein; C111729:Axin2 protein, mouse; D060509:Wnt3A Protein
keywords: DENTAL BIOLOGY; REPARATIVE DENTIN; RODENT MODEL; TOOTH INJURY; WNT/BETA CATENIN/LRP