Relative roles of osteoclast colony-stimulating factor and macrophage colony-stimulating factor in the course of osteoclast development.
Although recent studies have shown that osteopetrotic (op/op) mice lack macrophage colony-stimulating factor (M-CSF or CSF-1), the precise role of M-CSF in the development of immature osteoclasts remains unknown. Using a recently discovered osteoclast-specific colony-stimulating factor (O-CSF) and in vitro long-term bone marrow culture systems, we investigated the ability of op/op and control marrow stromal cells to support the production of O-CSF-responsive clonogenic osteoclast progenitors (colony-forming unit-osteoclast [CFU-O]) from inoculated normal stem cells. Remarkably, op/op stromal cell cultures produced five times as many nonadherent cells as control cultures throughout the experimental period of 14 weeks; an average of 37% of these cells were nonviable compared with 8% in control cultures. Significantly higher numbers of CFU-O were found in op/op cultures than in control cultures; the CFU-O in op/op and control cultures were proliferating at a similar rate. Higher numbers of calcitonin receptor-bearing cells were found when harvested cells from op/op flasks were cultured with 1,25(OH)2D3. These studies clearly show that op/op marrow stromal cells can support the differentiation and proliferation of osteoclast progenitors from inoculated stem cells and provide the first experimental evidence that M-CSF is not essential for the early stages of osteoclast development. We hypothesize that while O-CSF supports proliferation of osteoclast progenitors, M-CSF plays a role in the later development and maturation of the progenitor as well as in the prevention of cell death.
Lee
T H
TH
Department of Biological Structure, University of Washington School of Medicine, Seattle 98195.
Fevold
K L
KL
Muguruma
Y
Y
Lottsfeldt
J L
JL
Lee
M Y
MY
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000502:physiology; D001854:Bone Marrow Cells; D002117:Calcitriol / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D008221:Lymphoid Tissue / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D016173:Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010010:Osteoclasts / Q000737:chemistry / Q000166:cytology* / Q000502:physiology*; D010022:Osteopetrosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology* / Q000502:physiology*; D013997:Time Factors
D003115:Colony-Stimulating Factors; D017077:Culture Media, Conditioned; D016173:Macrophage Colony-Stimulating Factor; D002117:Calcitriol