Functions of the M-CSF receptor on osteoclasts.
Macrophage colony-stimulating factor (M-CSF) receptor has been previously reported to be present in osteoclasts both at mRNA and protein levels. However, the biochemical interactions between M-CSF and its receptor on osteoclasts are less well characterized than in mononuclear phagocytes. In this study, we show that (1) 125I-labeled M-CSF ligand specifically binds to the M-CSF receptor on osteoclasts by autoradiography; (2) binding of M-CSF to the receptor stimulates protein tyrosine phosphorylation in osteoclasts by immunostaining; (3) oxygen-derived free radicals produced by calvarial osteoclasts are increased by M-CSF stimulation (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 mouse calvarial osteoclasts are activated by M-CSF. These data suggest that under the conditions present in the calvarial model, M-CSF activates osteoclastic bone resorption.
Yang
S
S
Department of Pediatrics, Medical University of South Carolina, Charleston, USA.
Zhang
Y
Y
Rodriguiz
R M
RM
Ries
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WL
Key
L L
LL
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001862:Bone Resorption / Q000139:chemically induced; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism* / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011869:Radioligand Assay; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000633:toxicity; D014443:Tyrosine / Q000378:metabolism
D005609:Free Radicals; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D014443:Tyrosine; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor