Implication of Wnt signaling pathway in dental pulp progenitor differentiation

Objectives:

The goal of the present study was to analyze the mechanisms underlying the peptide action and to identify associated targets.

Methods:

For this purpose, we have exploited the properties of a pulpal progenitor cell line which, upon treatment by A-4, is recruited towards the odontoblastic phenotype. Indeed, culture in the presence of the peptide leads in 48h, to an activation of the matrix proteins DSP and DMP1 expression as shown by RT-PCR and western blot analysis. This activation is preceded by that of a series of transcription factors involved in embryonic tooth development.

Results:

We demonstrate that the Wnt signaling cascade is involved in the A-4-induced odontoblastic program: pulpal cell exposure to a Wnt inhibitor prevents the activation of DSP while treatment with a Wnt activator (BIO, 6-bromoindirubin-3'-oxime) mimicks the action of the peptide. In addition, the A-4 peptide finely modulates the expression of different Wnt actors. Finally, in vivo, implantation of BIO-loaded agarose beads in a rat molar leads to formation of a dentinal bridge.

Conclusions:

Altogether these results identify the Wnt canonic pathway as a signaling cascade recruited by A-4 involved in dental pulp progenitor differentiation towards the odontoblastic program. The amelogenin peptide A-4 may therefore constitute a potential molecule for regenerative therapies of the dentin.