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.
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19 July 1999
Brief Definitive Report|
July 19 1999
Vascular Endothelial Growth Factor Can Substitute for Macrophage Colony-Stimulating Factor in the Support of Osteoclastic Bone Resorption
Shumpei Niida,
Shumpei Niida
aFrom the Department of Anatomy, Hiroshima University School of Dentistry, Hiroshima 734-8553, Japan
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Masato Kaku,
Masato Kaku
bFrom the Department of Orthodontics, Hiroshima University School of Dentistry, Hiroshima 734-8553, Japan
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Hitoshi Amano,
Hitoshi Amano
cDepartment of Pharmacology, School of Dentistry, Showa University, Tokyo 142-8555, Japan
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Hisahiro Yoshida,
Hisahiro Yoshida
dDepartment of Molecular Genetics, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan
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Hiroshi Kataoka,
Hiroshi Kataoka
dDepartment of Molecular Genetics, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan
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Satomi Nishikawa,
Satomi Nishikawa
dDepartment of Molecular Genetics, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan
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Kazuo Tanne,
Kazuo Tanne
bFrom the Department of Orthodontics, Hiroshima University School of Dentistry, Hiroshima 734-8553, Japan
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Norihiko Maeda,
Norihiko Maeda
aFrom the Department of Anatomy, Hiroshima University School of Dentistry, Hiroshima 734-8553, Japan
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Shin-Ichi Nishikawa,
Shin-Ichi Nishikawa
dDepartment of Molecular Genetics, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan
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Hiroaki Kodama
Hiroaki Kodama
eResearch Center Kyoto, Bayer Yakuhin, Ltd., Kyoto 619-0216, Japan
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Shumpei Niida
aFrom the Department of Anatomy, Hiroshima University School of Dentistry, Hiroshima 734-8553, Japan
Masato Kaku
bFrom the Department of Orthodontics, Hiroshima University School of Dentistry, Hiroshima 734-8553, Japan
Hitoshi Amano
cDepartment of Pharmacology, School of Dentistry, Showa University, Tokyo 142-8555, Japan
Hisahiro Yoshida
dDepartment of Molecular Genetics, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan
Hiroshi Kataoka
dDepartment of Molecular Genetics, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan
Satomi Nishikawa
dDepartment of Molecular Genetics, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan
Kazuo Tanne
bFrom the Department of Orthodontics, Hiroshima University School of Dentistry, Hiroshima 734-8553, Japan
Norihiko Maeda
aFrom the Department of Anatomy, Hiroshima University School of Dentistry, Hiroshima 734-8553, Japan
Shin-Ichi Nishikawa
dDepartment of Molecular Genetics, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan
Hiroaki Kodama
eResearch Center Kyoto, Bayer Yakuhin, Ltd., Kyoto 619-0216, Japan
Received:
February 09 1999
Revision Requested:
May 19 1999
Accepted:
May 25 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 1999 The Rockefeller University Press
1999
The Rockefeller University Press
J Exp Med (1999) 190 (2): 293–298.
Article history
Received:
February 09 1999
Revision Requested:
May 19 1999
Accepted:
May 25 1999
Citation
Shumpei Niida, Masato Kaku, Hitoshi Amano, Hisahiro Yoshida, Hiroshi Kataoka, Satomi Nishikawa, Kazuo Tanne, Norihiko Maeda, Shin-Ichi Nishikawa, Hiroaki Kodama; Vascular Endothelial Growth Factor Can Substitute for Macrophage Colony-Stimulating Factor in the Support of Osteoclastic Bone Resorption. J Exp Med 19 July 1999; 190 (2): 293–298. doi: https://doi.org/10.1084/jem.190.2.293
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