The Role of Vascular Endothelial Growth Factor Receptors in Osteoclast Differentiation and Function.

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  2. Stephen Aldridge
  3. Professor Thomas Lennard
  4. John Williams
  5. Dr Mark Birch
Author(s)Aldridge SE, Lennard TWJ, Williams JR, Birch MA
Publication type Article
Journal Biochemical and Biophysical Research Communications
ISSN (print)0006-291X
ISSN (electronic)1090-2104
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Osteoclasts are derived from haematopoietic stem cell precursors of the monocyte/macrophage cell lineage, through interaction with factors that are believed to include M-CSF and RANKL. VEGF is a proangiogenic cytokine that has been shown to promote osteoclast differentiation and survival. In this study, we assessed the role of VEGF and its receptors in osteoclastogenesis, in vitro, by culturing osteoclast precursors in the presence of VEGF, VEGF receptor-specific ligands, and blocking antibodies to VEGF receptors. Activation of VEGFR1 in the presence of RANKL induces osteoclast differentiation. Stimulating the receptors individually induced increased resorption by osteoclasts compared to controls but not to the level observed when stimulating both receptors simultaneously. We have shown that VEGF induces osteoclast differentiation through its action on VEGFR1. The way in which VEGF mediates its effect on mature osteoclast activity, however, may be through its interaction with both receptor subtypes.
PubMed id16105658
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