OBJECTIVES: b-catenin, a critical molecule in the canonical Wnt signaling pathway, is expressed in mesenchymal cells during organogenesis. However, the role of b-catenin in odontogenesis is largely unknown, given that b-catenin null embryos die prior to gastrulation. The goal of this study was to determine the role of b-catenin in odontogenesis by targeted gene deletion of b-catenin in mice and overexpression of b-catenin in mesenchymal or pre-Od (odontoblast, 17IA4) or Od (17IIA11) cell lines. METHODS: Deletion of b-catenin in mesenchymal cells was generated by crossing the Dermo 1 (active in mesenchymal cells)-Cre mice with b-catenin floxed mice. Combinations of radiographs and histology were used to characterize the phenotype of b-catenin deletion in mesenchymal cells. Activation of b-catenin in mesenchymal (C3H10T1/2) or pre-Od (17IA4) or Od (17IIA11) cell lines was performed by addition of Wnt3a condition medium which activates b-catenin activity measured by TOPFLASH assay. Real-time RT-PCR, cell proliferation and mineralized nodule assays were performed for monitoring effects of b-catenin on cell behaviors. RESULTS: Deletion of b-catenin led to molar arrests and thinning of dentin in incisor in vivo. Activation of b-catenin had no effect on cell proliferation in all 3 cell lines, but increases alkaline phosphatase 3-fold in C3H10T1/2 cell line, 6.7-fold in pre-Od cell line, and 5.1-fold in Od cell line. Further, b-catenin increases levels of DMP1 and DSPP (two marker genes for odontogenesis) 3.8-fold and 4.2-fold in pre-Od cell line separately, but had very mild effect on both gene expressions in C3H10T1/2 or Od cell line. Finally, b-catenin significantly accelerated matrix mineralization in both pre-Od cell line (moderate) and Od cell line (strong). CONCLUSION: b-catenin signaling pathway has little effect on early cell proliferation but dramatically accelerates cell differentiation in pre-Od and odontoblast cells.  (Work supported by NIH grant: AR51587)

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