Molecular imaging of expression of vascular endothelial growth factor A (VEGF A) in femoral bone grafts transplanted into living mice Journal Article


Authors: Strachna, O.; Torrecilla, D.; Reumann, M. K.; Serganova, I.; Kim, J.; Gieschler, S.; Boskey, A. L.; Blasberg, R. G.; Mayer-Kuckuk, P.
Article Title: Molecular imaging of expression of vascular endothelial growth factor A (VEGF A) in femoral bone grafts transplanted into living mice
Abstract: The biology of cells transplanted with bone grafts is incompletely understood. Focusing on the early angiogenic response postgrafting, we report a mouse femur graft model in which grafts were derived from mice transgenic for a firefly luciferase (FLuc) bioluminescence reporter gene driven by a promoter for the angiogenic signaling molecule vascular endothelial growth factor (VEGF). Upon transplantation into wild-type (wt) mice, in vivo bioluminescence imaging (BLI) permitted longitudinal visualization and measurements of VEGF promoter activity in the transplanted graft cells and demonstrated a lag period of 7 days posttransplantation prior to robust induction of the promoter. To determine cellular mediators of VEGF induction in graft bone, primary graftderived osteoblastic cells (GDOsts) were characterized. In vitro BLI on GDOsts showed hypoxia-induced VEGF expression and that this induction depended on PI3K signaling and, to a lesser degree, on the MEK pathway. This transcriptional regulation correlated with VEGF protein production and was validated in GDOsts seeded on demineralized bone matrix (DBM), a bone graft substitute material. Together, combined imaging of VEGF expression in living animals and in live cells provided clues about the regulation of VEGF in cells post-bone grafting. These data are particularly significant toward the development of future smart bone graft substitutes. © 2014 Cognizant Comm. Corp.
Keywords: molecular imaging; osteoblasts; signaling pathways; bioluminescence imaging; vascular endothelial growth factor (vegf); bone grafting
Journal Title: Cell Transplantation
Volume: 23
Issue: 7
ISSN: 0963-6897
Publisher: Cognizant Communication Corporation  
Date Published: 2014-01-01
Start Page: 901
End Page: 912
Language: English
DOI: 10.3727/096368912x667015
PROVIDER: scopus
PUBMED: 23582187
PMCID: PMC5477423
DOI/URL:
Notes: Cell Transplant. -- Export Date: 8 July 2014 -- CODEN: CTRAE -- Source: Scopus
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  1. Ronald G Blasberg
    272 Blasberg