Chemerin-ChemR23 Signaling in Tooth Development

Objectives: Tissue-engineering approaches have been used to bioengineer many tissues such as skin, cornea, and bone. With respect to dental tissue regeneration, extensive prior studies have shown that coordinated and precise dental epithelial-mesenchymal (DE-DM) cell interactions guide natural dental tissue formation, emphasizing the importance of these interactions in regenerative dental therapeutics.  The goal of this study was to investigate potential roles for Chemerin/ChemR23 signaling in tooth development and regeneration. Ribosomal S6 phosphorylation (prS6) was used to evaluate Chemerin/ChemR23 signaling. 

Methods: Immunofuorescent (IF) microscopic analysis was used to evaluate Chemerin and ChemR23 expression in cultured DE and DM cells harvested from five-month-old porcine maxillary and mandibular third molar teeth. Western blotting and IF analyses were used to evaluate Runx2 and prS6 expression in Chemerin treated porcine dental cell cultures. Developmentally staged embryonic 12.5 days (E12.5), E14.5, E16.5, and postnatal day 1 (P1) mice were used to evaluate Chemerin, ChemR23, prS6, and Runx2 expression in natural tooth development via IF analyses. 

Results: Cultured porcine DE cells were found to express Chemerin and not ChemR23, while cultured porcine DM cells expressed ChemR23, and not Chemerin.  Chemerin treated DM cells expressed prS6 and Runx2 in a dose dependent manner.  Chemerin was detected in E12.5 DE, was not detectable in E14.5 or E16.5 teeth, and was detected in differentiated P1 stage ameloblasts (AM) and odontoblasts (OD).  In contrast, ChemR23 was first detected in E14.5 molar tooth DM, and in differentiating OD and AM in E16.5 and P1 stage teeth.  prS6 was detected in DE and DM tissues at all stages examined, in both progenitor cells, and in differentiated OD and AM.  

Conclusions:

These results suggest roles for ChemR23/Chemerin signaling in tooth development, and provide potential new targets for improved dental tissue regeneration. Supported by NIH/NIDCR DE016132 (PCY).