Immunolocalization of Vascular Endothelial Growth Factor During Heterotopic Bone Formation Induced From Grafted Periosteum

2004 ◽  
Vol 53 (2) ◽  
pp. 150-154 ◽  
Author(s):  
Takaaki Ueno ◽  
Toshimasa Kagawa ◽  
Miwa Kanou ◽  
Takashi Fujii ◽  
Joji Fukunaga ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Bone Formation ◽  
Heterotopic Bone ◽  
Vascular Endothelial ◽  
Heterotopic Bone Formation ◽  
Endothelial Growth Factor

scholarly journals A Comprehensive Clinicopathologic Analysis Suggests that Vascular Endothelial Growth Factor (VEGF) is the Most Likely Mediator of Periosteal New Bone Formation (PNBF) Associated with Diverse Etiologies

2008 ◽  
Vol 1 ◽  
pp. CMAMD.S442
Author(s):  
Meredith A. Lakey ◽  
Michael J. Klein ◽  
Ona M. Faye-Petersen
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Bone Formation ◽  
Fracture Repair ◽  
Prostaglandin E ◽  
Hypertrophic Osteoarthropathy ◽  
Vascular Endothelial ◽  
New Bone Formation ◽  
Endothelial Growth Factor ◽  
Periosteal New Bone Formation

Periosteal new bone formation (PNBF) is the means by which appositional bone growth normally takes place on the surfaces of compact bone. Alterations in the periosteal microenvironment trigger complex interactions between osteoblasts and endothelial cells to promote PNBF. Physiologic processes like mechanical stress result in normal PNBF; but, a variety of pathologic processes result in excessive PNBF. The production of sufficient bone to be detectable by conventional radiography is a common feature of diverse etiologies, including infection; inflammation; prostaglandin E2 administration for ductal-dependent congenital heart disease; metabolic and hormonal abnormalities; neoplasms; fracture repair; systemic hypoxia; and hypertrophic osteoarthropathy. While the clinical settings and distribution of affected bone sites in these conditions are different, the histopathology of the PNBF is essentially identical; so, it seems logical that a common pathway might mediate them all. By combining the observations and insights gained from osseous research and studying the clinical pathology of these diverse conditions, we constructed a comprehensive pathway to explain PNBF. In doing so, it seems likely that Vascular Endothelial Growth Factor (VEGF) is the most likely common mediator of the pathways that lead to PNBF.

scholarly journals Bone Morphogenetic Proteins Stimulate Angiogenesis through Osteoblast-Derived Vascular Endothelial Growth Factor A

Endocrinology ◽  
2002 ◽  
Vol 143 (4) ◽  
pp. 1545-1553 ◽  
Author(s):  
Martine M. L. Deckers ◽  
Rutger L. van Bezooijen ◽  
Geertje van der Horst ◽  
Jakomijn Hoogendam ◽  
Chris van der Bent ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Bone Formation ◽  
Bone Morphogenetic Proteins ◽  
Cross Talk ◽  
Osteoblast Differentiation ◽  
Angiogenic Factor ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Abstract During bone formation and fracture healing there is a cross-talk between endothelial cells and osteoblasts. We previously showed that vascular endothelial growth factor A (VEGF-A) might be an important factor in this cross-talk, as osteoblast-like cells produce this angiogenic factor in a differentiation-dependent manner. Moreover, exogenously added VEGF-A enhances osteoblast differentiation. In the present study we investigated, given the coupling between angiogenesis and bone formation, whether bone morphogenetic proteins (BMPs) stimulate osteoblastogenesis and angiogenesis through the production of VEGF-A. For this we used the murine preosteoblast-like cell line KS483, which forms mineralized nodules in vitro, and an angiogenesis assay comprising 17-d-old fetal mouse bone explants that have the ability to form tube-like structures in vitro. Treatment of KS483 cells with BMP-2, -4, and -6 enhanced nodule formation, osteocalcin mRNA expression, and subsequent mineralization after 18 d of culture. This was accompanied by a dose-dependent increase in VEGF-A protein levels throughout the culture period. BMP-induced osteoblast differentiation, however, was independent of VEGF-A, as blocking VEGF-A activity by a VEGF-A antibody or a VEGF receptor 2 tyrosine kinase inhibitor did not affect BMP-induced mineralization. To investigate whether BMPs stimulate angiogenesis through VEGF-A, BMPs were assayed for their angiogenic activity. Treatment of bone explants with BMPs enhanced angiogenesis. This was inhibited by soluble BMP receptor 1A or noggin. In the presence of a VEGF-A antibody, both unstimulated and BMP-stimulated angiogenesis were arrested. Conditioned media of KS483 cells treated with BMPs also induced a strong angiogenic response, which was blocked by antimouse VEGF-A but not by noggin. These effects were specific for BMPs, as TGFβ inhibited osteoblast differentiation and angiogenesis while stimulating VEGF-A production. These findings indicate that BMPs stimulate angiogenesis through the production of VEGF-A by osteoblasts. In conclusion, VEGF-A produced by osteoblasts in response to BMPs is not involved in osteoblast differentiation, but couples angiogenesis to bone formation.

scholarly journals Synergistic Effects of Vascular Endothelial Growth Factor on Bone Morphogenetic Proteins Induced Bone Formation In Vivo: Influencing Factors and Future Research Directions

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Bo Li ◽  
Hai Wang ◽  
Guixing Qiu ◽  
Xinlin Su ◽  
Zhihong Wu
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Bone Formation ◽  
Influencing Factors ◽  
Bone Morphogenetic Proteins ◽  
Synergistic Effects ◽  
Future Research ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) and bone morphogenetic proteins (BMPs), as key mediators in angiogenesis and osteogenesis, are used in a combined delivery manner as a novel strategy in bone tissue engineering. VEGF has the potential to enhance BMPs induced bone formation. Both gene delivery and material-based delivery systems were incorporated in previous studies to investigate the synergistic effects of VEGF and BMPs. However, their results were controversial due to variation of methods incorporated in different studies. Factors influencing the synergistic effects of VEGF on BMPs induced bone formation were identified and analyzed in this review to reduce confusion on this issue. The potential mechanisms and directions of future studies were also proposed here. Further investigating mechanisms of the synergistic effects and optimizing these influencing factors will help to generate more effective bone regeneration.

Adenovirus-mediated expression of vascular endothelial growth factor-a potentiates bone morphogenetic protein9-induced osteogenic differentiation and bone formation

2016 ◽  
Vol 397 (8) ◽  
pp. 765-775 ◽  
Author(s):  
Chang-jun Pi ◽  
Kai-lu Liang ◽  
Zhen-yong Ke ◽  
Fu Chen ◽  
Yun Cheng ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Bone Repair ◽  
Osteoporotic Fractures ◽  
Angiogenic Factor ◽  
Vascular Endothelial ◽  
Akt Inhibitor ◽  
Endothelial Growth Factor

Abstract Mesenchymal stem cells (MSCs) are suitable seed cells for bone tissue engineering because they can self-renew and undergo differentiation into osteogenic, adipogenic, chondrogenic, or myogenic lineages. Vascular endothelial growth factor-a (VEGF-a), an angiogenic factor, is also involved in osteogenesis and bone repair. However, the effects of VEGF-a on osteogenic MSCs differentiation remain unknown. It was previously reported that bone morphogenetic protein9 (BMP9) is one of the most important osteogenic BMPs. Here, we investigated the effects of VEGF-a on BMP9-induced osteogenesis with mouse embryo fibroblasts (MEFs). We found that endogenous VEGF-a expression was undetectable in MSCs. Adenovirus-mediated expression of VEGF-a in MEFs potentiated BMP9-induced early and late osteogenic markers, including alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). In stem cell implantation assays, VEGF-a augmented BMP9-induced ectopic bone formation. VEGF-a in combination with BMP9 effectively increased the bone volume and osteogenic activity. However, the synergistic effect was efficiently abolished by the phosphoinositide 3-kinase (PI3K)/AKT inhibitor LY294002. These results demonstrated that BMP9 may crosstalk with VEGF-a through the PI3K/AKT signaling pathway to induce osteogenic differentiation in MEFs. Thus, our findings demonstrate the effects of VEGF-a on BMP9-induced bone formation and provide a new potential strategy for treating nonunion fractures, large segmental bony defects, and/or osteoporotic fractures.

Optimizing combination of vascular endothelial growth factor and mesenchymal stem cells on ectopic bone formation in SCID mice

2017 ◽  
Vol 105 (12) ◽  
pp. 3326-3332 ◽  
Author(s):  
Chris H. Dreyer ◽  
Kristian Kjaergaard ◽  
Nicholas Ditzel ◽  
Niklas R. Jørgensen ◽  
Søren Overgaard ◽  
...  
Keyword(s):  
Stem Cells ◽  
Vascular Endothelial Growth Factor ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Bone Formation ◽  
Ectopic Bone Formation ◽  
Scid Mice ◽  
Vascular Endothelial ◽  
Ectopic Bone ◽  
Endothelial Growth Factor
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