OP-1 injection increases VEGF expression but not angiogenesis in a rabbit model of distraction osteogenesis.
We have previously shown that a single injection of rhBMP-7 (OP-1) applied to the regenerate early during distraction accelerates bone consolidation in a rabbit model of distraction osteogenesis. In the present study, we hypothesised that the injection of OP-1 improves bone consolidation by increasing blood flow to the distracted site. Blood flow into the regenerate of a rabbit model was measured and vascular endothelial growth factor (VEGF) expression was tested using semi-quantitative PCR. Immunohistochemistry was used for assessing the temporal and spatial expression of platelet endothelial cell adhesion molecule (PECAM), VEGF and its receptors following OP-1 injection. We observed a higher expression of VEGF and its receptors in the regenerate with OP-1 treatment. However, there was no difference in the increase in bone blood flow nor PECAM expression between the treated and control groups of animals. Interestingly, the increased expression of VEGF and its receptors was associated with chondrocyte and fibroblast-like cells, but not with endothelial cells. These results suggest that accelerated ossification by OP-1 may depend on a non-vascular mechanism, possibly involving a non-angiogenic function of VEGF signalling.
Mandu-Hrit
Manuela
M
Shriners Hospital for Children, Montreal, Canada.
Seifert
Erin
E
Kotsiopriftis
Maria
M
Lauzier
Dominique
D
Haque
Tasima
T
Rohlicek
Charles
C
Tabrizian
Maryam
M
Hamdy
Reggie C
RC
D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009389:Neovascularization, Pathologic; D010012:Osteogenesis; D019857:Osteogenesis, Distraction; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D012039:Regional Blood Flow; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A