title: Role of vascular endothelial growth factor in the communication between human osteoprogenitors and endothelial cells.
abstract: Proper bone remodeling requires an active process of angiogenesis which in turn supplies the necessary growth factors and stem cells. This tissue cooperation suggests a cross-talk between osteoblasts and endothelial cells. This work aims to identify the role of paracrine communication through vascular endothelial growth factor (VEGF) in co-culture between osteoblastic and endothelial cells. Through a well defined direct contact co-culture model between human osteoprogenitors (HOPs) and human umbilical vein endothelial cells (HUVECs), we observed that HUVECs were able to migrate along HOPs, inducing the formation of specific tubular-like structures. VEGF(165) gene expression was detected in the HOPs, was up-regulated in the co-cultured HOPs and both Flt-1 and KDR gene expression increased in co-cultured HUVECs. However, the cell rearrangement observed in co-culture was promoted by a combination of soluble chemoattractive factors and not by VEGF(165) alone. Despite having no observable effect on endothelial cell tubular-like formation, VEGF appeared to have a crucial role in osteoblastic differentiation since the inhibition of its receptors reduced the co-culture-stimulated osteoblastic phenotype. This co-culture system appears to enhance both primary angiogenesis events and osteoblastic differentiation, thus allowing for the development of new strategies in vascularized bone tissue engineering.
authors.affiliation: INSERM, U577, Bordeaux and Université Victor Segalen Bordeaux 2, UMR-S577, F-33076 Bordeaux Cedex, France. maritie.grellier@inserm.fr
authors.forename: Maritie
authors.initials: M
authors.lastname: Grellier
authors.forename: Nancy
authors.initials: N
authors.lastname: Ferreira-Tojais
authors.forename: Chantal
authors.initials: C
authors.lastname: Bourget
authors.forename: Reine
authors.initials: R
authors.lastname: Bareille
authors.forename: Fabien
authors.initials: F
authors.lastname: Guillemot
authors.forename: Joëlle
authors.initials: J
authors.lastname: Amédée
mesh_terms: D002450:Cell Communication; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D008855:Microscopy, Electron, Scanning; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D014470:Umbilical Cord / Q000166:cytology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor