The differentiation and functions of osteoclasts (OCs) are regulated by osteoblast-derived factors such as receptor activator of NF kappa; B ligand (RANKL) that stimulates OC formation and a novel secreted member of the TNF receptor superfamily, osteoprotegerin (OPG), that negatively regulates osteoclastogenesis. Preosteoclasts (pOCs) treated with RANKL became TRAP-positive OCs, which express vacuolar-type H (+) -ATPase and exhibit resorptive activity. Such effects of RANKL on pOCs are inhibited by OPG. OPG inhibits ruffled border formation in mature OCs, reduces their resorptive activity, and induces apoptosis.