Effects of vascular endothelial growth factor-C and -D on osteoclast differentiation and function in human peripheral blood mononuclear cells |
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| Authors: | Masahide Motokawa Natsumi Tsuka Masato Kaku Toshitsugu Kawata Tadashi Fujita Junji Ohtani Yayoi Matsuda Akiko Terao Kazuo Tanne |
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| Affiliation: | 1. Dept. of Molecular Microbiology and Immunology, St. Louis University, Saint Louis, MO, USA;2. Division of Bone and Mineral Disease, Department of Medicine, Washington University in St. Louis, Saint Louis, MO, USA;1. Department of Orthopaedic and Spinal Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan;2. Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo, Japan;3. Section of Regenerative Therapeutics for Spine and Spinal Cord, Tokyo Medical and Dental University, Tokyo, Japan;1. MIMR-PHI Institute of Medical Research, Clayton, VIC, Australia;2. Department of Human Biosciences, La Trobe University, Bundoora, VIC, Australia;3. Barwon Biomedical Research, Department of Medicine, The Geelong Hospital, Geelong, VIC, Australia;4. School of Medicine, Deakin University, Geelong, VIC, Australia;5. Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia;6. Department of Orthopaedics, St Vincent''s Hospital, Fitzroy, VIC, Australia;7. Department of Surgery, St Vincent''s Hospital, Fitzroy, VIC, Australia |
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| Abstract: | ![]()
ObjectiveThe 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).DesignPBMCs 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.ResultsRANKL 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.ConclusionsThis 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. |
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