Transient recruitment of osteoclasts and expression of their function in osteopetrotic (op/op) mice by a single injection of macrophage colony‐stimulating factor

Abstract Severe deficiency of osteoclasts in op/op mice, caused by the absence of functional macrophage colony‐stimulating factor (M‐CSF), is cured by daily injections of purified recombinant human M‐CSF (rhM‐CSF). In this study, we found that a single injection of 5 μ g rhM‐CSF is enough for recruitment of osteoclasts in mutant mice. Osteoclast number increased during the period between 2 and 4 days after the single rhM‐CSF injection. When YM175, a new derivative of bisphosphonate, was administered to the mice 4 days after rhM‐CSF injection or later, osteoclasts disappeared by 3 days after YM175 administration. However, a significant number of osteoclasts were detected even at 3 days after YM175 administration when YM175 was administered 3 days after rhM‐CSF injection or earlier. These results indicate that YM175 is cytotoxic only to functioning osteoclasts and that recruitment of osteoclasts is finished 4 days after a single rhM‐CSF injection. The osteoclasts actively resorbed bone trabeculae for a prolonged period, demonstrating that M‐CSF is not requisite for the functioning of mature osteoclasts.