It is broadly accepted that only osteoclasts are responsible for bone resorption. On the other hand, ameloblastoma is the most common odontogenic tumor and it is thought that receptor activated NF-kappa B ligand (RANKL) released from ameloblastoma cells activates osteoclast formation and bone resorption. Thus, ameloblastoma cells might be involved in pathological bone resorption. In addition, we have identified that ameloblastoma cells (AM-1) also dissolve bone mineral by activation of vacuolar-type H+-ATPase (V- ATPase) localized on the plasma membrane.
To clarify the mechanisms of pathologic bone demineralization including clinical manifestation of dental root absorption by ameloblastoma cells.
OsteologicTM, a hydroxyapatite coated disc, was used for examination of bone mineral absorption. Immunocytochemistry was performed with a Carl Zeiss confocal microscopy, LSM510.
Absorption of hydroxyapatite by AM-1 cells was observed after 7 to 10 days culture on OsteologicTM. In contrast, the human keratinocyte, HaCaT, did not show any absorption. After absorption, AM-1 promoted cell death in the same manner as osteoclasts. These effects were inhibited by bafilomycin (1 nM), a V-ATPase specific inhibitor. Immunocytochemistry of V-ATPase a3 subunit in AM-1 showed localization on the plasma membrane. Further, co-localization of ClC-7, the Cl-/H+ antiporter, with V-ATPase was also observed similar to osteoclast. Western blot analysis revealed relatively high expression of V-ATPase a3 subunit in AM-1 compared with HaCaT cells.
These results suggest that ameloblastoma cells, which originate from epithelia, aberrantly demineralize bone and dental roots by cooperating with osteoclasts.
Keywords: Ameloblastoma, Epithelium/epithelial and Mineralization