Macrophage colony stimulating factor restores in vivo bone resorption in the op/op osteopetrotic mouse.
The op/op variant of murine osteopetrosis is a recessive mutation characterized by impaired bone resorption due to lack of osteoclasts. Cultured osteoblasts and fibroblasts from this mutant do not secrete M-CSF activity and resident macrophages are absent in bone marrow. This failure has been related to a mutation within the M-CSF coding region. We report now that the administration of recombinant human M-CSF (rhM-CSF) corrects in vivo the impaired bone resorption in this animal. The treatment restores the bone marrow cavity virtually absent in the op/op animal and induces the appearance of resorbing osteoclasts and of resident bone marrow macrophages. This proves that the deficiency of M-CSF is the cause of the op/op bone disorder and that this cytokine is directly or indirectly necessary for physiological osteoclastogenesis, the resulting bone resorption and for the establishment of bone marrow hemopoiesis.
Felix
R
R
Department of Pathophysiology, University of Berne, Switzerland.
Cecchini
M G
MG
Fleisch
H
H
D000818:Animals; D001862:Bone Resorption; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D005260:Female; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000473:pathology; D008297:Male; D008663:Metacarpus / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000473:pathology; D010022:Osteopetrosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D016186:Receptor, Macrophage Colony-Stimulating Factor; D013997:Time Factors
D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor