title: Vascular endothelial growth factor improves bone repair in a murine nonunion model.
abstract: OBJECTIVE
  Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that plays an important role during skeletal development and fracture healing. Previous experimental studies have shown that VEGF applied immediately after injury can stimulate bone repair in animal fracture nonunion models. However, the effectiveness of VEGF on an established fracture non-union has not been determined. the goal of this work was to test the ability of VEGF applied at a later stage on the healing of fracture nonunions.
  
  
  METHODS
  In this study, a murine non-union model was induced by rapid distraction of a tibia osteotomy. this model exhibits radiological and histological evidence of impaired fracture healing at 7 days after the completion of distraction. VEGF (10 µg in 20 µl Pbs/day, n=10) or control (20 µl Pbs/day, n=10) was injected directly into the distraction gap through the posterior musculature on three consecutive days (7, 8, and 9 days after completing distraction). A third group of animals (n=10) with rapid distraction, but no injections, served as non-treated controls. Fracture healing was analyzed by x-ray, histology, and histomorphometry at 27 days after the last round of distraction.
  
  
  RESULTS
  radiographs showed that half of the VEGF treated animals (5/10) achieved bony healing whereas the majority of Pbs treated (7/10) and non-treated controls (8/10) did not exhibit bone bridging. Histological and histomorphometric analyses demonstrated that VEGF increased, but not significantly, the amount of bone formed in the distraction gap (1.35 ± 0.35 mm(3)), compared to the saline treated (0.77 ± 0.25 mm(3), p=0.19) and non-treated animals (0.79 ± 0.23mm(3), p=0.12).
  
  
  CONCLUSIONS
  Results from this study demonstrate that VEGF potentially promotes bone repair, warranting further research in this direction.
authors.affiliation: Department of Orthopedic Surgery, Orthopaedic Trauma Institute, University of California at San Francisco, San Francisco, CA 94110, USA.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Ogilvie
authors.forename: Chuanyong
authors.initials: C
authors.lastname: Lu
authors.forename: Ralph
authors.initials: R
authors.lastname: Marcucio
authors.forename: Mark
authors.initials: M
authors.lastname: Lee
authors.forename: Zachary
authors.initials: Z
authors.lastname: Thompson
authors.forename: Diane
authors.initials: D
authors.lastname: Hu
authors.forename: Jill A
authors.initials: JA
authors.lastname: Helms
authors.forename: Theodore
authors.initials: T
authors.lastname: Miclau
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D017102:Fracture Healing / Q000187:drug effects*; D005599:Fractures, Ununited / Q000188:drug therapy*; D008297:Male; D051379:Mice; D013977:Tibia / Q000187:drug effects* / Q000293:injuries; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D043925:Angiogenesis Inducing Agents; D042461:Vascular Endothelial Growth Factor A
keywords: VEGF; Vascular Endothelial Growth Factor; delayed union; distraction osteogenesis; fracture; non-union