Alendronate inhibits osteoclastogenesis and calcium ionophore antagonizes the effects of alendronate

Objective: To study the effect of alendronate(ALN) on osteoclastogenesis and bone resorption function and the antagonistic effect of calcium lonophore(CL) against ALN.Methods: Osteoclasts(OCs) were cultured by induction of mouse monocyte-macrophage cell line-RAW264.7.The OCs were divided into 4 groups: control(A),ALN-treated(B),ALN+CL-treated(C) and calcium lonophore-treated(D).At day 6 of treatment,osteoclastogenesis and resorption function of OCs were examined by TRAP staining and SEM observation respectively.The expressions of NFATc1 and c-Fos genes and protein were detected by RT-PCR and Western-blot respectively.Results: TRAP positive multinuclear cells were observed and resorption lacunas were formed in all 4 groups.Highest number of TRAP positive multinuclear cells and largest size of resorption lacunaes were observed in group D,followed in turn by group C,A and B.The highest expressions of NFATc1 and c-Fos mRNA and protein were found in group D,followed by group C,A and B(A vs B,C or D,P0.01).Conclusion: ALN can inhibit osteoclastogenesis and resorption function of OCs,down-regulate gene expression of NFATc1 and c-Fos in OCs.Calcium lonophore has an antagonistic effect against ALN and the effect is associated with the regulation of ion intracellular Ca2+ level.