The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/7/293/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 2, July 19, 1999 293-298


Brief Definitive Report

Vascular Endothelial Growth Factor Can Substitute for Macrophage Colony-Stimulating Factor in the Support of Osteoclastic Bone Resorption

Shumpei Niidaa, Masato Kakub, Hitoshi Amanoc, Hisahiro Yoshidad, Hiroshi Kataokad, Satomi Nishikawad, Kazuo Tanneb, Norihiko Maedaa, Shin-Ichi Nishikawad, and Hiroaki Kodamae

a From the Department of Anatomy, Hiroshima University School of Dentistry, Hiroshima 734-8553, Japan
b From the Department of Orthodontics, Hiroshima University School of Dentistry, Hiroshima 734-8553, Japan
c Department of Pharmacology, School of Dentistry, Showa University, Tokyo 142-8555, Japan
d Department of Molecular Genetics, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan
e Research Center Kyoto, Bayer Yakuhin, Ltd., Kyoto 619-0216, Japan
Department of Anatomy, Hiroshima University School of Dentistry, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.81-82-257-562181-82-257-5621

sniida{at}ipc.hiroshima-u.ac.jp

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.

Key Words: osteoclasts • vascular endothelial growth factor • vascular endothelial growth factor receptor • macrophage colony-stimulating factor • osteopetrosis


© 1999 The Rockefeller University Press


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