title: Vascular endothelial growth factors and receptors are up-regulated during development of apical periodontitis.
abstract: BACKGROUND
  Apical periodontitis is a common inflammatory disease caused by persistent root canal infection and is characterized by bone resorption. Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) have been described in many pathologic and inflammatory conditions, but their involvement in the development of apical periodontitis has not been thoroughly investigated. The aim of this study was to quantify gene expression and localize VEGF-A, VEGF-C, and VEGF-D and VEGFR-2 and VEGFR-3 in a rat model of apical periodontitis.
  
  
  METHODS
  Molar pulps were unilaterally exposed to the oral cavity for 10 or 21 days. Jaw sections were used for localization of VEGFs and VEGFRs with immunohistochemistry and identification of cells with double immunofluorescence. Gene expression analysis for VEGF-A, VEGF-C, and VEGFR-3 of periapical tissues was performed with quantitative real-time polymerase chain reaction.
  
  
  RESULTS
  All investigated factors and receptors were expressed immunohistochemically in blood vessels at the periodontal ligament of control teeth and were up-regulated during lesion development. In apical lesions, macrophages and neutrophils expressed all studied factors and receptors, with macrophages being an important source of VEGF-C and VEGF-D. Osteoclasts expressed VEGFR-2 and VEGFR-3, and the latter was also identified in fibroblast-like cells in the lesions. VEGF-A and VEGFR-3 gene expression was up-regulated at days 10 and 21 (P < .05).
  
  
  CONCLUSIONS
  The current findings indicate that the VEGF family and receptors are involved in vascular remodeling and immune functions during disease development. The presence of VEGFR-2 and VEGFR-3 on osteoclasts indicates that bone resorbing activity is influenced by VEGFs.
authors.affiliation: Institute of Biomedicine, Faculty of Medicine-Dentistry, University of Bergen, Bergen, Norway. Nancy.Bletsa@biomed.uib.no
authors.forename: Athanasia
authors.initials: A
authors.lastname: Bletsa
authors.forename: Anca
authors.initials: A
authors.lastname: Virtej
authors.forename: Ellen
authors.initials: E
authors.lastname: Berggreen
mesh_terms: D000818:Animals; D003789:Dental Pulp Exposure / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D010485:Periapical Periodontitis / Q000378:metabolism* / Q000473:pathology; D010486:Periapical Tissue / Q000378:metabolism / Q000473:pathology; D010513:Periodontal Ligament / Q000098:blood supply; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D040262:Receptors, Vascular Endothelial Growth Factor / Q000032:analysis*; D012391:Root Resorption / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis; D042643:Vascular Endothelial Growth Factor D / Q000032:analysis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000032:analysis
chemical_list: D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; C467498:vascular endothelial growth factor A, rat; D040262:Receptors, Vascular Endothelial Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3