title: Meloxicam temporally inhibits the expression of vascular endothelial growth factor receptor (VEGFR)-1 and VEGFR-2 during alveolar bone repair in rats.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF) plays an important role during angiogenesis and bone repair. This study investigated whether the use of meloxicam alters bone repair via downregulation of VEGF and receptor expression.
  
  
  METHODS
  One hundred twenty male Wistar rats had their maxillary right incisor extracted. Animals were divided into a control group (CG; n = 60) and a meloxicam-treated group (TG; n = 60) that received either a single daily intraperitoneal injection of 0.9% NaCl or meloxicam 3 mg/kg, respectively, for 7 consecutive days. Alveolar bone repair was evaluated histomorphometrically, whereas VEGF and its receptors were analyzed by immunohistochemistry and quantitative polymerase chain reaction (qPCR). Data were submitted to two-way analysis of variance and Tukey post hoc test with P < 0.05.
  
  
  RESULTS
  Bone volume density increased significantly (P = 0.001) in both groups with a strong correlation between treatment and periods (P = 0.003). In the TG, a small amount of bone formation occurred compared with the CG between 3 and 21 days. No significant differences in the number of VEGF-positive cells per square millimeter (P = 0.07) and VEGF messenger RNA (mRNA) expression (P = 0.49) were found between groups. Immunostained cells per square millimeter and mRNA expression for VEGF receptor (VEGFR)-1 (P = 0.04 and P < 0.001) and VEGFR-2 (P < 0.001 for both analysis) showed a strong interaction between treatment groups and periods. In the TG, immunostained cells per square millimeter and mRNA expression for VEGFR-1 were, respectively, 89% and 37% lower from 3 to 10 days compared with the CG, whereas for VEGFR-2, these values were 252% and 60%, respectively, from 3 to 7 days.
  
  
  CONCLUSIONS
  In rat alveolar bone repair, meloxicam did not affect VEGF expression but downregulated VEGFR expression, which may cause a delay in the bone repair/remodeling process.
authors.affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil.
authors.forename: Ricardo Vinicius Nunes
authors.initials: RV
authors.lastname: Arantes
authors.forename: Tania Mary
authors.initials: TM
authors.lastname: Cestari
authors.forename: Bruno Alvares
authors.initials: BA
authors.lastname: Viscelli
authors.forename: Thiago José
authors.initials: TJ
authors.lastname: Dionísio
authors.forename: Gustavo Pompermaier
authors.initials: GP
authors.lastname: Garlet
authors.forename: Carlos Ferreira
authors.initials: CF
authors.lastname: Santos
authors.forename: Gerson Francisco
authors.initials: GF
authors.lastname: de Assis
authors.forename: Rumio
authors.initials: R
authors.lastname: Taga
mesh_terms: D000539:Alveolar Process / Q000187:drug effects*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015536:Down-Regulation; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D008437:Maxilla / Q000187:drug effects; D000077239:Meloxicam; D010010:Osteoclasts / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D013997:Time Factors; D020390:Tooth Socket / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000187:drug effects*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D007527:Isoenzymes; D013843:Thiazines; D013844:Thiazoles; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C000602029:Kdr protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077239:Meloxicam
keywords: Cyclooxygenase 2 inhibitors; tooth socket; vascular endothelial growth factor A.