title: Effects of vascular endothelial growth factor on osteoblasts and osteoclasts.
abstract: BACKGROUND
  Bone remodeling is crucial to the success of many dental procedures and is tightly regulated. Vascular endothelial growth factor (VEGF), a key cytokine for angiogenesis, is also an important regulator of bone remodeling. We aimed to examine the mechanisms by which VEGF induces bone remodeling by studying its effects on cultured osteoblasts and osteoclasts.
  
  
  METHODS
  Preosteoblastic MC3T3-E1 cells were treated with vehicle or VEGF-A165. Cell proliferation, migration, and invasion potentials were assessed. Preosteoclastic RAW264.7 cells were treated with vehicle or VEGF with or without the receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoclast formation was measured with tartrate-resistant acid phosphatase staining. Conditioned media from vehicle-treated or VEGF-treated MC3T3-E1 cells were tested for the levels of RANKL and osteoprotegerin (OPG) and were used to treat RAW264.7 cells to observe osteoclast formation.
  
  
  RESULTS
  VEGF significantly induced MC3T3-E1 cell proliferation, migration, and invasion. VEGF did not directly induce osteoclastogenesis but significantly increased the RANKL/OPG ratio in the conditioned media from the MC3T3-E1 cultures; this significantly increased osteoclast formation.
  
  
  CONCLUSIONS
  VEGF stimulates osteoclast differentiation by increasing the osteoblastic RANKL/OPG ratio but has no direct effect on osteoclast precursor cells, and it induces osteoblast proliferation, migration, and invasion potentials in vitro.
authors.affiliation: Assistant professor, Department of Orthodontics and Pediatric Dentistry, School of Dental Medicine, State University of New York at Stony Brook, Stony Brook, NY. Electronic address: hechang.huang@sbumed.org.
authors.forename: Hechang
authors.initials: H
authors.lastname: Huang
authors.affiliation: Research assistant professor, Department of Orthodontics and Pediatric Dentistry, School of Dental Medicine, State University of New York at Stony Brook, Stony Brook, NY.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Professor and chair, Department of Orthodontics and Pediatric Dentistry, School of Dental Medicine, State University of New York at Stony Brook, Stony Brook, NY.
authors.forename: Stephanos
authors.initials: S
authors.lastname: Kyrkanides
mesh_terms: D016475:3T3 Cells; D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects; D002452:Cell Count; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004396:Coloring Agents; D017077:Culture Media, Conditioned; D007527:Isoenzymes / Q000032:analysis; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects*; D010010:Osteoclasts / Q000187:drug effects*; D053244:Osteoprotegerin / Q000032:analysis; D053245:RANK Ligand / Q000032:analysis / Q000494:pharmacology; D000071681:Tartrate-Resistant Acid Phosphatase; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D004396:Coloring Agents; D017077:Culture Media, Conditioned; D007527:Isoenzymes; D053244:Osteoprotegerin; D053245:RANK Ligand; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase