Macrophage Colony-Stimulating Factor Increases Bone Resorption by Osteoclasts Disaggregated From Human Fetal Long Bones

Macrophage colony-stimulating factor (M-CSF) is known to play an important role in human and murine osteoclast formation. Although M-CSF has been shown to inhibit isolated neonatal rat osteoclasts from resorbing bone, its action on the mature human osteoclast has not been described. We now report that M-CSF increases osteoclastic bone resorption in a dose-responsive manner. Bone resorption by mature human fetal osteoclasts, including pit area, depth, and volume, was increased in the presence of M-CSF compared with vehicle. The number of osteoclasts in the cultures was similar after 2 and 18 h in the presence of M-CSF, whereas there was a significant reduction in osteoclast number, whether assessed as the number of tartrate-resistant acid phosphatase (TRAP)-positive or vitronectin receptor-positive cells after 18 h in M-CSF-free cultures. The number of nuclei per osteoclast after 2 or 18 h in M-CSF was also similar and there was no difference in the number of vitronectin receptor-positive mononucleate cells at 2 and 18 h. This suggests that the increased bone resorption is likely to be accounted for by enhanced osteoclast survival in M-CSF compared with controls rather than by formation of new osteoclasts.