Osteogenic genes related to the canonic WNT pathway are down-regulated in ameloblastoma

Abstract

Objective: The aim of this study was to determine the expression of essential osteogenic genes related to the canonic WNT pathway, i.e., WDR5, sFRP-2, and their downstream genes, in ameloblastoma and to clarify their biologic impact on this neoplasm.

Study design: Forty-six paraffin-embedded ameloblastoma samples and ameloblastic (AM-1) and preosteoblastic (KUSA/A1) cell lines were used. Immunohistochemistry, Western blot, reverse-transcription polymerase chain reaction, and alkaline phosphatase (ALP) activity assay were performed.

Results: WDR5, essential for osteoblast differentiation and canonic WNT pathway activation, was negative in most ameloblastoma cases and weakly expressed in AM-1 cells. Conversely, sFRP-2s was overexpressed. RUNX2 and C-MYC, downstream inductions of canonic WNT pathway activation, demonstrated weak mRNA expressions in ameloblastoma, suggesting WNT pathway impairment and WDR5 functional inactivity. Recombinant WDR5 weakly induced ALP activity of KUSA/A1 cells cultured in AM-1 conditioned medium.

Conclusions: These findings suggest that WNT-related bone-forming genes are down-regulated in ameloblastoma. Concurrent sFRP-2 overexpression suggests that both bone-forming and bone-inhibiting genes equally contributed to reduced bone formation in this neoplasm.