title: Effects of vascular endothelial growth factor-C and -D on osteoclast differentiation and function in human peripheral blood mononuclear cells.
abstract: OBJECTIVE
  The purpose of this study was to clarify the interaction of vascular endothelial growth factors (VEGFs)-C and -D with cell surface foetal liver kinase-1 (Flk-1) and fms-like tyrosine kinase-4 (Flt-4) receptors in the induction and activity of osteoclasts in cultured human peripheral blood mononuclear cells (PBMCs).
  
  
  METHODS
  PBMCs were cultured on chamber slides or on ivory discs for 2 or 3 weeks in the presence of macrophage-colony stimulating factor (M-CSF), VEGF-A, -C or -D, or placental growth factor (PlGF) with or without receptor activator of nuclear factor kappa-B ligand (RANKL). The number of osteoclasts in each group was counted and the area of ivory resorption was measured. In addition, osteoclast differentiation was further analysed under the same conditions, but with the addition of specific neutralizing antibodies against Flk-1 and Flt-4.
  
  
  RESULTS
  RANKL was essential for the induction of osteoclasts in PBMCs. However, significant differences were found in the number of osteoclasts induced by VEGF-A, -C, -D or M-CSF with RANKL compared with control groups lacking or containing RANKL. Blocking of either Flk-1 or Flt-4 resulted in a reduction in the enhancement of osteoclast differentiation in PBMCs by VEGF-C or -D with RANKL. The osteoclasts induced by VEGF-A, -C, -D or M-CSF with RANKL formed significantly larger resorption lacunae than those formed by osteoclasts induced by RANKL alone.
  
  
  CONCLUSIONS
  This study showed that VEGF-C and -D play a role in the induction of osteoclast differentiation through both Flk-1 and Flt-4 receptors and influence the area of the ivory resorption in PBMCs.
authors: Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. motumo@hiroshima-u.ac.jp
authors: Masahide
authors: M
authors: Motokawa
authors: Natsumi
authors: N
authors: Tsuka
authors: Masato
authors: M
authors: Kaku
authors: Toshitsugu
authors: T
authors: Kawata
authors: Tadashi
authors: T
authors: Fujita
authors: Junji
authors: J
authors: Ohtani
authors: Yayoi
authors: Y
authors: Matsuda
authors: Akiko
authors: A
authors: Terao
authors: Kazuo
authors: K
authors: Tanne
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D001862:Bone Resorption / Q000473:pathology; D002452:Cell Count; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000494:pharmacology; D053245:RANK Ligand / Q000494:pharmacology; D000071681:Tartrate-Resistant Acid Phosphatase; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D042582:Vascular Endothelial Growth Factor C / Q000494:pharmacology*; D042643:Vascular Endothelial Growth Factor D / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000187:drug effects; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000187:drug effects
chemical_list: D015415:Biomarkers; D006133:Growth Substances; D007527:Isoenzymes; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D000072483:Placenta Growth Factor; D016173:Macrophage Colony-Stimulating Factor; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase