title: Adenovirus-mediated VEGF-A gene transfer induces bone formation in vivo.
abstract: Osteoporosis is a major problem in elderly population. We tested the hypothesis whether vascular endothelial growth factor (VEGF-A) gene transfer is an appropriate way to enhance bone formation and recruitment of osteoblasts in vivo. Adenovirus vectors containing VEGF-A or lacZ cDNAs (1.4x10(10) pfu) were injected locally into right distal femurs of New Zealand White rabbits. Saline was injected into all contralateral distal femurs. One and three weeks after the gene transfers femurs were collected for analyses. X-Gal staining showed that up to 20% of the bone marrow cells were transfected although gene transfer also resulted in biodistribution of the vector and expression of the transgene in liver and spleen. Trabecular bone hard tissue histomorphometry of the distal femurs was performed to analyze the effect of gene transfer on bone turnover. When compared with unilateral lacZ transfected trabecular bone at one-week and three-week time points, VEGF-A gene transfer significantly increased bone formation parameters, such as osteoblast number, osteoid volume, and bone volume. Also, bone resorption surface was greatly reduced. It is concluded that injection of adenovirus vector can transfect bone marrow cells in vivo with a relatively high efficiency. Our results suggest that adenovirus-mediated VEGF-A gene transfer induces bone formation via increasing osteoblast activity and may be useful for the treatment of osteoporosis and other diseases that require efficient osteogenic therapy.
authors.affiliation: A. I. Virtanen Institute, University of Kuopio, Kuopio, Finland.
authors.forename: Mikko Olavi
authors.initials: MO
authors.lastname: Hiltunen
authors.forename: Markku
authors.initials: M
authors.lastname: Ruuskanen
authors.forename: Jouni
authors.initials: J
authors.lastname: Huuskonen
authors.forename: Anssi Juhani
authors.initials: AJ
authors.lastname: Mähönen
authors.forename: Mari
authors.initials: M
authors.lastname: Ahonen
authors.forename: Juha
authors.initials: J
authors.lastname: Rutanen
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kosma
authors.forename: Anitta
authors.initials: A
authors.lastname: Mahonen
authors.forename: Heikki
authors.initials: H
authors.lastname: Kröger
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001853:Bone Marrow / Q000000981:diagnostic imaging; D001842:Bone and Bones / Q000033:anatomy & histology; D002460:Cell Line; D016228:Endothelial Growth Factors / Q000235:genetics*; D005822:Genetic Vectors; D008954:Models, Biological; D010012:Osteogenesis; D011817:Rabbits; D011859:Radiography; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D016228:Endothelial Growth Factors; D042461:Vascular Endothelial Growth Factor A; D001616:beta-Galactosidase