University of Oulu

Effects of vascular endothelial growth factor (VEGF-A) and endostatin on bone

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Author: Sipola, Annina1
Organizations: 1University of Oulu, Faculty of Medicine, Institute of Biomedicine, Department of Anatomy and Cell Biology
Format: ebook
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.5 MB)
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Language: English
Published: 2009
Publish Date: 2009-11-24
Thesis type: Doctoral Dissertation
Defence Note: Academic dissertation to be presented with the assent of the Faculty of Medicine of the University of Oulu for public defence in Auditorium A101 of the Department of Anatomy and Cell Biology (Aapistie 7 A), on 4 December 2009, at 2 p.m.
Reviewer: Professor Heikki Kröger
Professor George Sándor


Angiogenesis is essential for the replacement of cartilage by bone during skeletal growth and regeneration. Vascular endothelial growth factor-A (VEGF-A) is a key regulator of angiogenesis whereas endostatin, a potent inhibitor of endothelial cell proliferation and migration, is a natural antagonist of VEGF-A. The regulatory roles of these peptides in angiogenesis, bone formation and bone cells were investigated in this study.

In the present work we studied the effects of VEGF-A, delivered with an adenoviral vector, on the recovery of bone drilling defects in rat femur. Our data confirm the important role of VEGF in bone healing and that adenoviral VEGF gene transfer may modify bone defect healing in a rodent model.

We studied the effects of VEGF-A and endostatin on bone resorption activity. It was found that VEGF-A is a potent stimulator of bone resorption and osteoclast differentiation in vitro and endostatin can antagonize this stimulatory effect when acting directly on bone cells. This suggests that endostatin is indeed a regulator of bone resorption, but not a critical one.

In the present study we induced ectopic bone formation in the hamstring muscles of adult mice. The effects of VEGF-A and endostatin in the ectopic bone formation assay were evaluated by the simultaneous delivery of both peptides with recombinant adenoviral vectors. It was found that endostatin retards the cartilage phase in endochondral ossification that subsequently reduces bone formation. We conclude that bone growth and healing, which share features with ectopic bone formation, may be regulated by endostatin.

To confirm in vivo effects on bone formation we further investigated the effects of endostatin and VEGF-A on mouse pre-osteoblastic cells in vitro. Finally the effects of endostatin on bone were studied in transgenic mouse lines overexpressing endostatin, and mice lacking collagen XVIII.

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Series: Acta Universitatis Ouluensis. D, Medica
ISSN-E: 1796-2234
ISBN: 978-951-42-9318-4
ISBN Print: 978-951-42-9317-7
Issue: 1034
Copyright information: © University of Oulu, 2009. This publication is copyrighted. You may download, display and print it for your own personal use. Commercial use is prohibited.