Rapid publication: Impairment of macrophage colony-stimulating factor production and lack of resident bone marrow macrophages in the osteopetrotic op/op Mouse

Abstract

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.

Integration of T‐cell receptor, Notch and cytokine signals programs mouse γδ T‐cell effector differentiation

“…We therefore used primary mouse embryonic fibroblasts (MEF) derived from BALB/c mice (H2 d haplotype, T10 + T22 − ) 26 to generate T10, T10+DL4, T10+T22, and T10+T22+DL4 cell lines (Fig. S2).…”

Induction of Functional Human Macrophages from Bone Marrow Promonocytes by M-CSF in Humanized Mice

“…The role of M-CSF in monocyte development, however, is more controversial. Early studies reported that the number of monocytes was reduced in the blood of M-CSF-deficient mice probably because of a deficiency of osteoclasts that are required to maintain a functional BM microenvironment (2,4,10,(26)(27)(28). A later study showed that M-CSF was critical for the survival of circulating monocytes in the periphery (29).…”

VEGF, FLT3 ligand, PlGF and HGF can substitute for M-CSF to induce human osteoclast formation: implications for giant cell tumour pathobiology

“…These findings suggest that these growth factors may have a role in compensating for the absence of M-CSF in op/op mice, which have a mutation in the coding region of the M-CSF gene that results in an osteopetrotic phenotype. 6,7 It is known that a few osteoclasts can be identified in bones of these osteopetrotic mice and that this defect, can partially correct itself with age. 14,15 The above growth factors may thus provide a salvage pathway for osteoclast formation that could explain this observation.…”

“…5 The importance of M-CSF in osteoclast formation is evidenced by the fact that in op/op osteopetrotic mice, which have a mutation in the M-CSF gene, very few osteoclasts are found in bone and there is markedly decreased bone resorption. 6,7 M-CSF promotes several aspects of osteoclastogenesis including the proliferation and fusion of osteoclast precursors as well as osteoclasts and the expression of the RANKL receptor by these cells. [8][9][10] The effect of M-CSF on mature osteoclast resorption activity is controversial with both a decrease and increase in lacunar resorption being reported.…”