Vascular endothelial growth factor can substitute for macrophage colony-stimulating factor in the support of osteoclastic bone resorption.
We demonstrated previously that a single injection of recombinant human macrophage colony-stimulating factor (rhM-CSF) is sufficient for osteoclast recruitment and survival in osteopetrotic (op/op) mice with a deficiency in osteoclasts resulting from a mutation in M-CSF gene. In this study, we show that a single injection of recombinant human vascular endothelial growth factor (rhVEGF) can similarly induce osteoclast recruitment in op/op mice. Osteoclasts predominantly expressed VEGF receptor 1 (VEGFR-1), and activity of recombinant human placenta growth factor 1 on osteoclast recruitment was comparable to that of rhVEGF, showing that the VEGF signal is mediated through VEGFR-1. The rhM-CSF-induced osteoclasts died after injections of VEGFR-1/Fc chimeric protein, and its effect was abrogated by concomitant injections of rhM-CSF. Osteoclasts supported by rhM-CSF or endogenous VEGF showed no significant difference in the bone-resorbing activity. op/op mice undergo an age-related resolution of osteopetrosis accompanied by an increase in osteoclast number. Most of the osteoclasts disappeared after injections of anti-VEGF antibody, demonstrating that endogenously produced VEGF is responsible for the appearance of osteoclasts in the mutant mice. In addition, rhVEGF replaced rhM-CSF in the support of in vitro osteoclast differentiation. These results demonstrate that M-CSF and VEGF have overlapping functions in the support of osteoclastic bone resorption.
Niida
S
S
Department of Anatomy, Hiroshima University School of Dentistry, Hiroshima 734-8553, Japan. sniida@ipc.hiroshima-u.ac.jp
Kaku
M
M
Amano
H
H
Yoshida
H
H
Kataoka
H
H
Nishikawa
S
S
Tanne
K
K
Maeda
N
N
Nishikawa
S
S
Kodama
H
H
D000818:Animals; D001862:Bone Resorption / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008222:Lymphokines / Q000494:pharmacology* / Q000502:physiology; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D010010:Osteoclasts / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D010022:Osteopetrosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D011994:Recombinant Proteins / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016173:Macrophage Colony-Stimulating Factor