Dose- and time-dependent changes in osteoclast induction after a single injection of vascular endothelial growth factor in osteopetrotic mice

Abstract

Osteopetrotic (op/op) mice have a severe deficiency of osteoclasts, monocytes, and macrophages caused by the absence of functional macrophage-colony stimulating factor (M-CSF). It is also well known that the number of osteoclasts in op/op mice exhibits a gradual increase naturally, demonstrating the self-healing of osteopetrosis. Our recent study showed that osteoclasts in normal mice expressed fms-like tyrosine kinase (Flt-1), the receptor for VEGF, and that recombinant human VEGF (rh VEGF) induced a significant number of osteoclasts in op/op mice. In this study, we confirmed that a single injection of 5 μg rh VEGF was sufficient to recruite osteoclasts in the femora of op/op mice. However, the number of osteoclasts recruited by rh VEGF was less than that by rhM-CSF. The number of osteoclasts reached to a maximum level three days after the injection of rh VEGF or rhM-CSF. We found that Flt-1 was expressed in the osteoclasts induced by rh VEGF injection as well as in naturally appeared osteoclasts in op/op mice. These results indicate that the osteoclast precursor can differentiate to mature osteoclast at least three days after rh VEGF injection and the stimulatory potency of rh VEGF is lower than that of rhM-CSF.