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The dose of growth factors influences the synergistic effect of vascular endothelial growth factor on bone morphogenetic protein 4-induced ectopic bone formation

Li, G and Corsi-Payne, K and Zheng, B and Usas, A and Peng, H and Huard, J (2009) The dose of growth factors influences the synergistic effect of vascular endothelial growth factor on bone morphogenetic protein 4-induced ectopic bone formation. Tissue Engineering - Part A, 15 (8). 2123 - 2133. ISSN 1937-3341

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Abstract

Although vascular endothelial growth factor (VEGF) has been shown to act synergistically with bone morphogenetic protein (BMP)2 and BMP4 to promote ectopic endochondral bone formation via cell-based BMP gene therapy, the optimal ratio of VEGF to either of the BMPs required to obtain this beneficial effect remains unclear. In the current study, two cell types (C2C12, NIH/3T3) were retrovirally transduced to express BMP4 only or both BMP4 and VEGF. The resulting groups of cells were tested for their cellular proliferation, in vitro mineralization capacity, survival potential, and ability to undergo ectopic bone formation when implanted into a gluteofemoral muscle pocket created in severe combined immunodeficient mice. Results showed that VEGF inhibited the in vitro calcification of C2C12 and NIH/3T3 cells transduced to express BMP4. In vivo, C2C12 and NIH/3T3 cells expressing BMP4 and VEGF displayed significantly less bone formation than the same cells expressing only BMP4. In vivo, our results indicated that, when the ratio of VEGF to BMP4 is high, a detrimental effect on ectopic bone formation is observed; however, when the ratio is kept low and constant over time, the detrimental effect that VEGF has on ectopic bone formation is lost. Our studies revealed that VEGF's synergistic role in BMP4 induced ectopic bone formation is dose and cell-type dependent, which is an important consideration for cell-based gene therapy and tissue engineering for bone healing. © 2009 Mary Ann Liebert, Inc.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Li, G
Corsi-Payne, K
Zheng, B
Usas, A
Peng, H
Huard, J
Centers: Other Centers, Institutes, Offices, or Units > Stem Cell Research Center
Date: 1 August 2009
Date Type: Publication
Journal or Publication Title: Tissue Engineering - Part A
Volume: 15
Number: 8
Page Range: 2123 - 2133
DOI or Unique Handle: 10.1089/ten.tea.2008.0214
Schools and Programs: School of Medicine > Anesthesiology
Refereed: Yes
ISSN: 1937-3341
MeSH Headings: Animals; Bone Morphogenetic Protein 4--pharmacology; Calcification, Physiologic--drug effects; Cell Proliferation--drug effects; Cell Survival--drug effects; Chondrogenesis--drug effects; Choristoma--pathology; Dose-Response Relationship, Drug; Drug Synergism; Genetic Engineering; Humans; Immunohistochemistry; Mice; NIH 3T3 Cells; Osteogenesis--drug effects; Retroviridae--genetics; Transduction, Genetic; Vascular Endothelial Growth Factor A--pharmacology
Other ID: NLM NIHMS148534, NLM PMC2811054
PubMed Central ID: PMC2811054
PubMed ID: 19215221
Date Deposited: 09 Apr 2014 16:32
Last Modified: 29 Jan 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/21056

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