A role for cell-surface CSF-1 in osteoblast-mediated osteoclastogenesis.
CSF-1 is required for osteoblast-mediated osteoclast formation. Osteoblasts produce soluble (sCSF-1) and cell-surface forms of CSF-1 (also known as membrane-bound CSF-1, mCSF-1) but their individual contributions to osteoclastogenesis remain unclear. Using glutaraldehyde-fixed primary murine osteoblasts as a source of mCSF-1, osteoblasts from op/op mice as a source for other osteoblast-derived osteoclastogenic factors and murine bone marrow as a source of osteoclast progenitors, osteoclast-like cells (OCL) formation was observed after 7-9 days of co-culture. In contrast, no OCL formation occurred when mCSF-1 expressed by primary murine osteoblasts was blocked by CSF-1 antibody pretreatment or when op/op osteoblasts were substituted for primary murine osteoblasts in the co-culture system. Osteoclast formation was also significantly inhibited when murine primary osteoblasts were pretreated with an antisense phosphorothioate oligonucleotide against mCSF-1. Finally, mCSF-1 and sCSF-1 were synergistic in stimulating OCL formation. These data support the conclusion that mCSF-1 plays an important role in osteoblast-mediated osteoclastogenesis within the bone microenvironment.
Yao
G-Q
GQ
Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Sun
B H
BH
Weir
E C
EC
Insogna
K L
KL
D000818:Animals; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D016376:Oligonucleotides, Antisense; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology
D016376:Oligonucleotides, Antisense; D016173:Macrophage Colony-Stimulating Factor