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Wnt Acts as a Prosurvival Signal to Enhance Dentin Regeneration
Author(s) -
Hunter Daniel J,
Bardet Claire,
Mouraret Sylvain,
Liu Bo,
Singh Gurpreet,
Sadoine Jérémy,
Dhamdhere Girija,
Smith Andrew,
Tran Xuan Vinh,
Joy Adrienne,
Rooker Scott,
Suzuki Shigeki,
Vuorinen Annukka,
Miettinen Susanna,
Chaussain Catherine,
Helms Jill A
Publication year - 2015
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.2444
Subject(s) - wnt signaling pathway , regeneration (biology) , microbiology and biotechnology , dentin , signal transduction , biology , dentistry , medicine
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. © 2015 American Society for Bone and Mineral Research.