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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2017: 3.022

CiteScore 2017: 2.81

SCImago Journal Rank (SJR) 2017: 1.562
Source Normalized Impact per Paper (SNIP) 2017: 0.705

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1437-4315
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Volume 397, Issue 8

Issues

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

Chang-jun Pi
  • Department of Orthopedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, People’s Republic of China
  • Other articles by this author:
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/ Kai-lu Liang
  • Department of Orthopedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, People’s Republic of China
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/ Zhen-yong Ke
  • Department of Orthopedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, People’s Republic of China
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/ Fu Chen
  • Department of Orthopedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, People’s Republic of China
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/ Yun Cheng
  • Department of Orthopedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, People’s Republic of China
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/ Liang-jun Yin
  • Department of Orthopedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, People’s Republic of China
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/ Zhong-liang Deng
  • Department of Orthopedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, People’s Republic of China
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/ Bai-cheng He
  • Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing 400016, People’s Republic of China
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/ Liang Chen
  • Corresponding author
  • Department of Orthopedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, People’s Republic of China
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Published Online: 2016-03-21 | DOI: https://doi.org/10.1515/hsz-2015-0296

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)

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About the article

Received: 2015-12-02

Accepted: 2016-03-11

Published Online: 2016-03-21

Published in Print: 2016-08-01


Citation Information: Biological Chemistry, Volume 397, Issue 8, Pages 765–775, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2015-0296.

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