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.

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 Role of Vascular Endothelial Growth Factor (VEGF) in Human Embryo Implantation: Clinical Implications

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 253
Author(s):  
Xi Guo ◽  
Hong Yi ◽  
Tin Chiu Li ◽  
Yu Wang ◽  
Huilin Wang ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Recurrent Miscarriage ◽  
Embryo Implantation ◽  
Critical Role ◽  
Angiogenic Factor ◽  
Vascular Endothelial ◽  
Underlying Mechanisms ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is a well-known angiogenic factor that plays a critical role in various physiological and pathological processes. VEGF also contributes to the process of embryo implantation by enhancing embryo development, improving endometrial receptivity, and facilitating the interactions between the developing embryo and the endometrium. There is a correlation between the alteration of VEGF expression and reproductive failure, including recurrent implantation failure (RIF) and recurrent miscarriage (RM). In order to clarify the role of VEGF in embryo implantation, we reviewed recent literature concerning the expression and function of VEGF in the reproductive system around the time of embryo implantation and we provide a summary of the findings reported so far. We also explored the effects and the possible underlying mechanisms of action of VEGF in embryo implantation.

scholarly journals Effect of directly acting anti-viral agents on immunological imprints in chronic HCV-4a patients: interleukin-10 and vascular endothelial growth factor genes expression level

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Iman S. Naga ◽  
Amel Abdel Fattah Kamel ◽  
Said Ahmed Ooda ◽  
Hadeer Muhammad Fath Elbab ◽  
Rania Mohamed El-Sharkawy
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Growth Factor ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Growth Factor ◽  
Angiogenic Factor ◽  
Vascular Endothelial ◽  
Wide Range ◽  
Chronic Hcv ◽  
Endothelial Growth Factor

Abstract Background Hepatitis C virus infection is a global health challenge with Egypt being one of the highly affected countries. IL-10 has been suggested as a suitable marker to assess necroinflammation and to monitor the progression of liver damage. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor playing a central role in many physiological as well as pathological processes. Several factors can be predictive of the response to treatment and achievement of SVR; some of which are host-related, and others are virus-related. The gene expression of IL-10 and VEGF have multiple effects for treatment response. The aim of the present work was to study the effect of treatment with directly acting agents (DAA) on the expression of VEGF and IL-10 genes in chronic hepatitis C virus-infected Egyptian genotype-4a patients. Twenty-five HCV subjects where evaluated for IL-10 and VEGF gene expression before and after treatment with DAA. Results IL-10 expression was downregulated in 92% of the cases. VEGF expression was heterogeneous showing spreading of values along a wide range with 64% of the cases being downregulated. Conclusion DAAs do not completely reverse the immunological imprints established upon chronic HCV infection.

P0590ADVERSE RENAL OUTCOME FOLLOWING ADMINISTRATION OF INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS IN A SINGLE TERTIARY CENTRE IN MALAYSIA

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Maisarah Jalalonmuhali ◽  
Tengku Ain Fathlun Tengku Kamalden ◽  
Nurul 'Ain Sham Ismail ◽  
See Yen Yong ◽  
Wei Ting Teo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Serum Creatinine ◽  
Post Treatment ◽  
Angiogenic Factor ◽  
Renal Outcome ◽  
Vascular Endothelial ◽  
Anti Vegf ◽  
Endothelial Growth Factor

Abstract Background and Aims Intravenous (IV) anti-vascular endothelial growth factor(VEGF) is a potent anti-angiogenic factor for the treatment of solid tumours. While, intravitreal anti-VEGF injection is used in the treatment for macular and retinal diseases. The effects of IV anti-VEGF agents are well documented to cause hypertension, renal impairment and proteinuria. However only few reports showed the significance of intravitreal anti-VEGF injection causing minimal change disease (MCD) and acute kidney injury (AKI). Hence, this study is to determine the outcome of renal function following intravitreal anti-VEGF injection. Method This is a prospective, cross sectional study recruiting patients from ophthalmology day-care operation theatre that were scheduled for intravitreal anti-VEGF injection in University Malaya Medical Centre (UMMC). On the day of the injection of anti-VEGF, patients’ demographic data (age, gender, medical background, medications), blood pressure, height, weight and investigations for serum creatinine and urine protein creatinine ratio (PCR) were collected. Following these, they will receive the intravitreal anti-VEGF as per schedule. All these patients were given a follow-up within 72hours to reassess blood pressure, serum creatinine and urine PCR. Results A total of 90 patients were recruited. However, 15 patients were subsequently excluded as there was no repeated serum creatinine at 72-hours post treatment. Their mean age was 67.25 ± 10.41. Among all, 3 patients had significance increased in serum creatinine (4%) with significance changed of urine PCR post treatment. Table 1 showed baseline parameters prior to treatment and table 2 was post treatment parameters. Higher serum creatinine and proteinuria pre intravitreal anti-VEGF were identified to have higher OR of 1.018 (95% CI 1.001-1.035) (p=0.043) and OR 1.004 (1.000-1.007) (p=0.025) respectively among those who developed AKI. In assessing the association between higher pre-treatment creatinine and proteinuria (independent variable) and development of AKI (dependent variable) estimated by logistic regression with no AKI as a reference group we found that there were no significance. Conclusion Following intravitreal anti-VEGF administration, there were no significant changes in blood pressure. However, 4% from our cohort had AKI and worsening proteinuria at 72 hours post treatment. These patients had higher serum creatinine and proteinuria prior to treatment. However, our study is underpowered to establish the relationship between intravitreal anti-VEGF and development of AKI. Further study with larger sample size and longer-term outcome is needed.

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 Vascular Endothelial Growth Factor Is the Major Angiogenic Factor in Omentum: Mechanism of the Omentum-Mediated Angiogenesis

1997 ◽  
Vol 67 (2) ◽  
pp. 147-154 ◽  
Author(s):  
Qing-Xue Zhang ◽  
Christopher J. Magovern ◽  
Charles A. Mack ◽  
Kurt T. Budenbender ◽  
Wilson Ko ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Angiogenic Factor ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor
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