Impairment of macrophage colony-stimulating factor production and lack of resident bone marrow macrophages in the osteopetrotic op/op mouse.
Mouse calvaria-derived osteoblastlike cells have been shown to produce macrophage colony-stimulating factor (M-CSF). This factor may be involved in osteoclastogenesis and thus in bone resorption. In the present study we investigated whether the production of M-CSF was altered in the osteopetrotic mouse mutant strain op/op, characterized by a decrease in osteoclast number and an impairment of bone resorption. Whole calvariae and cells, as well as skin and lung fibroblasts, of the op/op mouse were found to produce no measurable M-CSF, in contrast to tissue and cells derived from normal littermates. M-CSF was identified by colony assay in semisolid media and by inhibition of the biologic activity with antiserum against M-CSF. Furthermore, the number of resident macrophages, identified by F4/80 antigen (F4/80 Ag) immunohistochemistry, was drastically decreased in bone and bone marrow of the op/op mouse, but in skin these cells were normal in number and morphology. These findings suggest that both M-CSF and resident macrophages play a role in the mechanism of bone resorption. The op/op mouse appears to be a valuable model to further investigate such a hypothesis.
Department of Pathophysiology, University of Berne, Switzerland.
R
R
Felix
M G
MG
Cecchini
W
W
Hofstetter
P R
PR
Elford
A
A
Stutzer
H
H
Fleisch
D000818:Animals; D000911:Antibodies, Monoclonal; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor; D008264:Macrophages / Q000473:pathology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009500:Neutralization Tests; D010022:Osteopetrosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000166:cytology / Q000378:metabolism; D012886:Skull / Q000166:cytology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D003115:Colony-Stimulating Factors; D016173:Macrophage Colony-Stimulating Factor