Inhibitory action of bisphosphonates on bone resorption does not involve the regulation of RANKL and OPG expression

Abstract

OCLs, osteoclast-like cells; 1,25-(OH)2VitD3, 1,25-dihydroxyvitaminD3 The mechanism of inhibitory action of bisphospho-nates on bone resorption is not fully elucidated. Osteoclast formation and activity are regulated by osteoblast-derived factors such as the osteoclast dif-ferentiating factor, receptor activator of NF-kappaB ligand (RANKL) and the inhibitor, osteoprotegerin (OPG). To investigate in vitro effects of bisphospho-nates on mouse osteoblastic cells, we examined the expression levels of RANKL and OPG in the cells treated with alendronate or pamidronate (10-8~10-5 M) alone, or combined with 10 nM of 1,25-(OH)2VitD3 for 24 or 48 h. Various concentrations of alendronate and pamidronate did not change the mRNA expres-sion of RANKL and OPG consistently irrespective of 1,25-(OH)2VitD3 presence. When added into coc-ultures of mouse osteoblastic cells and bone mar-row cells, both alendronate and pamidronate inhibited osteoclast formation and bone resorption but failed to alter the RANKL and OPG mRNA expression. These results indicate that the inhibi-tion of bone resorption by bisphosphonates is not mediated by the regulation of RANKL and OPG expression