Human receptor activator of NF-κB ligand (RANKL) induces osteoclastogenesis of primates in vitro

Mouse receptor activator of NF-??B ligand (RANKL), which induces osteoclastogenesis from monocytes or macrophages, was independently cloned by three groups in 1997. Mouse osteoclasts have been induced from peripheral monocytes stimulated by RANKL and macrophage colony-stimulating factor (M-CSF) both in vitro and in vivo; however, the mechanism of primate osteoclastogenesis has not been studied. In addition, the effects of human RANKL on primate osteoclastogenesis remain to be elucidated. Here, we investigated the effect of human RANKL on the osteoclastogenesis of monocytes from five subspecies of primates. Human RANKL induced osteoclastogenesis of all the primates. In addition, human RANKL induced pit formation by osteoclasts from monocytes of the crab-eating macaque. We also demonstrated that the primate osteoclastogenesis was inhibited by a novel peptide, which inhibited human osteoclastogenesis in our previous study. Thus, these findings clearly demonstrated that human RANKL induces primate osteoclastogenesis in the presence of human M-CSF.