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

  • Chang-jun Pi , Kai-lu Liang , Zhen-yong Ke , Fu Chen , Yun Cheng , Liang-jun Yin , Zhong-liang Deng , Bai-cheng He and Liang Chen EMAIL logo
Published/Copyright: March 21, 2016
Biological Chemistry
From the journal Biological Chemistry Volume 397 Issue 8

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.

Keywords: bone repair; mesenchymal stem cells (MSCs); phosphoinositide 3-kinase (PI3K)

Acknowledgments

The authors thank the Department of Pharmacology, School of Pharmacy, at Chongqing Medical University for providing the facilities used for this study. We also thank the Natural Science Foundation Project of Chongqing Science and Technology Commission (cstc2011jjzt0063).

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Received: 2015-12-2
Accepted: 2016-3-11
Published Online: 2016-3-21
Published in Print: 2016-8-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Endocytosis of pro-inflammatory cytokine receptors and its relevance for signal transduction
  4. The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction
  5. Research Articles/Short Communications
  6. Genes and Nucleic Acids
  7. Genetic association of NAD(P)H quinone oxidoreductase (NQO1*2) polymorphism with NQO1 levels and risk of diabetic nephropathy
  8. Protein Structure and Function
  9. Troponins, intrinsic disorder, and cardiomyopathy
  10. Molecular Medicine
  11. Molecular mechanisms mediating the beneficial metabolic effects of [Arg4]tigerinin-1R in mice with diet-induced obesity and insulin resistance
  12. Cell Biology and Signaling
  13. Adenovirus-mediated expression of vascular endothelial growth factor-a potentiates bone morphogenetic protein9-induced osteogenic differentiation and bone formation
  14. Proteolysis
  15. The intact Kunitz domain protects the amyloid precursor protein from being processed by matriptase-2
  16. Novel Techniques
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https://doi.org/10.1515/hsz-2015-0296
Keywords for this article
bone repair; mesenchymal stem cells (MSCs); phosphoinositide 3-kinase (PI3K)

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Endocytosis of pro-inflammatory cytokine receptors and its relevance for signal transduction
  4. The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction
  5. Research Articles/Short Communications
  6. Genes and Nucleic Acids
  7. Genetic association of NAD(P)H quinone oxidoreductase (NQO1*2) polymorphism with NQO1 levels and risk of diabetic nephropathy
  8. Protein Structure and Function
  9. Troponins, intrinsic disorder, and cardiomyopathy
  10. Molecular Medicine
  11. Molecular mechanisms mediating the beneficial metabolic effects of [Arg4]tigerinin-1R in mice with diet-induced obesity and insulin resistance
  12. Cell Biology and Signaling
  13. Adenovirus-mediated expression of vascular endothelial growth factor-a potentiates bone morphogenetic protein9-induced osteogenic differentiation and bone formation
  14. Proteolysis
  15. The intact Kunitz domain protects the amyloid precursor protein from being processed by matriptase-2
  16. Novel Techniques
  17. A systematic comparison of two new releases of exome sequencing products: the aim of use determines the choice of product
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