Expression of Wnt5a in tooth germs and the related signal transduction analysis

ObjectiveWnt5a is generally considered a non-canonical Wnt family member and plays an important role in the development of several tissues through regulation of cell fate, proliferation, migration, polarity and death. This study investigates its expression mode in human tooth development and the involved cell signal transduction pathways, as they remain unclear.DesignThe expression of Wnt5a was analyzed by immunohistochemistry method. Recombinant adenovirus encoding full-length Wnt5a cDNA was constructed to investigate four cell signal pathways and nine dentinogenesis nuclear transcription factors in response to Wnt5a in human dental papilla cells (HDPCs).ResultsImmunostaining revealed that Wnt5a was expressed in enamel epithelium cells from the bud stage, and in odontoblast layers and dental papilla tissues from early bell stage of human tooth development onward. Western blot analysis indicated that p42/44 MAPK, p38 MAPK, JNK and AKT signal pathways could be phosphorylated by WNT5A. RT-PCR analysis showed that Wnt5a increased the expression of DLX1, DLX2, LEF1, MSX2, PAX9 and RUNX2 mRNA, but decreased BARX1 and PITX2 mRNA.ConclusionsIt was concluded that WNT5A is expressed in human tooth development, and that p42/44 MAPK, p38 MAPK, JNK and AKT signal pathways and DLX1, DLX2, LEF1, MSX2, PAX9, RUNX2 could be activated by Wnt5a.