Aluminum-fluoride complexes induce osteoclastogenesis

Abstract

Receptor activator of NF-kB ligand (RANKL)-induced osteoclastogenesis is accompanied by Ca2+ signaling which sequentially activates calcineurin and NFATc1 and triggers osteoclastogenesis. However, it is not known whether RANKL-independent Ca2+ signaling could be induced and activates differentiation of osteoclasts during osteoclastogenesis. In the present study, the effect of aluminum-fluoride complexes, a G-protein activator, on Ca2+ signaling and osteoclastogenesis in mouse leukemic macrophage cell line, RAW 264.7 cells, and primary cultured mouse bone marrow derived macrophages was investigated. Using micro-CT and toluidine blue staining, decreased bone density was observed in the group of mice exposed to aluminum-fluoride complexes in drinking water for eight weeks. Aluminum-fluoride complexes induced the generation of extracellular Ca2+-dependent intracellular Ca2+concentration ([Ca2+]i) oscillations. Moreover, aluminum-fluoride complexes enhanced the generation of RANKL-mediated TRAP positive osteoclasts and induced the activated MAPK signaling such as ERK and JNK proteins. These results suggest that G-protein activation by aluminum-fluoride complexes could induce [Ca2+]i oscillations and osteoclast differentiation in osteoclast precursor cells.