Adenoviral VEGF-A gene transfer induces angiogenesis and promotes bone formation in healing osseous tissues.
BACKGROUND
Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. VEGF has been safely and efficiently applied to stimulate neovascularization in ischemic tissues in atherosclerotic patients. VEGF has an important role in bone repair by promoting angiogenesis and by stimulating major skeletal cell populations, chondrocytes, osteoblasts and osteoclasts.


METHODS
We studied the effect of VEGF-A on the recovery of bone drilling defects in rat femur delivered with first-generation adenoviral vector. The virus was injected into the muscle layer surrounding the bone defect made by drilling and the healing was followed for 1, 2, and 4 weeks.


RESULTS
The VEGF effect was first demonstrated with an increased number of FVIII-related antigen-positive blood vessels in the defect area 1 week after the procedure. The proportional area of remaining reparative tissue was significantly reduced in the VEGF-treated animals 2 weeks after the injury suggesting favorable effect on bone healing. Increased periosteal cartilage was seen at the early phases of healing suggesting endochondral ossification. VEGF overexpression, however, completed the endochondral phase earlier compared with the control condition. Bone mineral content was enhanced in the VEGF-treated femurs measured with peripheral quantitative computed tomography at a 2-week time point.


CONCLUSIONS
Our data confirm the important role of VEGF in bone healing. We show for the first time that adenoviral VEGF-A gene transfer may modify bone defect healing in a rodent model.
Tarkka
Tatu
T
Department of Surgery, University of Tampere, Finland.
Sipola
Annina
A
Jämsä
Timo
T
Soini
Ylermi
Y
Ylä-Herttuala
Seppo
S
Tuukkanen
Juha
J
Hautala
Timo
T
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000098:blood supply; D005264:Femoral Fractures / Q000473:pathology / Q000628:therapy*; D017102:Fracture Healing / Q000502:physiology*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D008297:Male; D018919:Neovascularization, Physiologic; D010012:Osteogenesis; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat