[RANKL signaling and bone diseases. Quiescent osteoclast precursors and RANKL signaling].

It is well known that bone marrow macrophages differentiate into osteoclasts in response to M-CSF and RANKL in culture. However, the characteristics and dynamics of osteoclast precursors in vivo are not clear. Cell cycle arrest in osteoclast precursors is a prerequisite step for their differentiation into osteoclasts. We named such precursors "QOPs (cell cycle-arrested quiescent osteoclast precursors) " . Injection of 2MD [a potent analogue of 1α, 25 (OH) (2)D(3)] , RANKL, or M-CSF to mice induced osteoclast differentiation from QOPs. Moreover, osteoclasts appearing in BMP (bone morphogenetic protein) -induced ectopic bone were also differentiated from QOPs without cell proliferation. These results indicate that (1)osteoclasts are formed from QOPs in response to bone resorbing stimuli in vivo, (2) QOPs circulate in the bloodstream and settle in the right place for osteoclastogenesis. Here I review recent advances in our understanding of osteoclast precursors in vivo.