Interrelationship Between SHH and TGF-beta in the Formation of Odontomas

The SHH signaling regulates cell proliferation in the ectomesenchyme, thus controlling tooth morphogenesis, while TGF-ß and bone morphogenetic proteins (BMPs) have been associated with reactionary and reparative dentinogenesis. The aim of this study was to investigate the role of signaling proteins in odontogenesis and odontoma formation. In this retrospective cross-sectional study, we analyzed the immunohistochemical expression of TGF-ß, BMP4, and SHH pathway proteins in 23 compound odontomas, 21 complex odontomas, and 17 tooth germs. The results demonstrated immunoexpression of BMP4, especially in the ectomesenchyme of complex odontomas (median=33.7; P <0.001). SHH was more immunoexpressed in the epithelium of tooth germs ( P <0.001) and in the ectomesenchyme of complex odontomas ( P =0.029). Similarly, TGF-ß exhibited higher immunoexpression in the epithelium of tooth germs ( P <0.001) and in the ectomesenchyme of complex odontomas ( P =0.002). SHH was more immunoexpressed in the ectomesenchyme of odontomas and in the inner enamel epithelium of tooth germs. Furthermore, SHH and BMP4 were significantly correlated. In developing teeth, the highest concentrations of these proteins were found in the odontogenic epithelium during the bud and cap stages. Differential expression occurred mainly in the ectomesenchyme of tumors, indicating that this component is indeed more proliferative.