Macrophage colony-stimulating factor (M-CSF) receptor has been previou
sly reported to be present in osteoclasts both at mRNA and protein lev
els, However, the biochemical interactions between M-CSF and its recep
tor on osteoclasts are less well characterized than in mononuclear pha
gocytes. In this study, we show that (1) I-125-labeled M-CSF ligand sp
ecifically binds to the M-CSF receptor on osteoclasts by autoradiograp
hy; (2) binding of M-CSF to the receptor stimulates protein tyrosine p
hosphorylation in osteoclasts by immunostaining; (3) oxygen-derived fr
ee radicals produced by calvarial osteoclasts are increased by M-CSF s
timulation (1.37 +/- 0.08, n = 10, p < 0.01); and (4) bone resorption
in calvarial explants is enhanced by M-CSF (1.153 +/- 0.09, n = 10, p
< 0.001), Thus, our data provide multiple lines of evidences that mous
e calvarial osteoclasts are activated by M-CSF, These data suggest tha
t under the conditions present in the calvarial model, M-CSF activates
osteoclastic bone resorption.