Osteoblasts stimulated with pulsed electromagnetic fields increase HUVEC proliferation via a VEGF-A independent mechanism

Richard A. Hopper, Jon P. Verhalen, Oren M. Tepper, Babek J. Mehrara, Robert Detch, Edward I. Chang, Samuel Baharestani, Bruce J. Simon, Geoffrey C. Gurtner

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The clinically beneficial effect of low frequency pulsed electromagnetic fields (ELF-PEMF) on bone healing has been described, but the exact mechanism of action remains unclear. A recent study suggests that there is a direct autocrine mitogenic effect of ELF-PEMF on angiogenesis. The hypothesis of this study is that ELF-PEMF also has an indirect effect on angiogenesis by manipulation of vascular endothelial growth factor (VEGF)-A-based paracrine intercellular communication with neighboring osteoblasts. Conditioned media experiments measured fetal rat calvarial cell (FRC) and human umbilical vein endothelial cell (HUVEC) proliferation using tritiated thymidine uptake. We demonstrate that ELF-PEMF (15 Hz, 1.8 mT, for 8 h) has an indirect effect on the proliferation rate of both endothelial cells and osteoblasts in vitro by altering paracrine mediators. Conditioned media from osteoblast cells stimulated with ELF-PEMF increased endothelial proliferation 54-fold, whereas media from endothelial cells stimulated with ELF-PEMF did not affect osteoblast proliferation. We examined the role of the pro-angiogenic mediator VEGF-A in the mitogenic effect of ELF-PEMF- stimulated osteoblast media on endothelial cells. The production of VEGF-A by FRC as measured by ELISA was not changed by exposure to PEMF, and blocking experiments demonstrated that the ELF-PEMF-induced osteoblast-derived endothelial mitogen observed in these studies was not VEGF- A, but some other soluble angiogenic mediator. Bioelectromagnetics 30:189-197, 2009.

Original languageEnglish (US)
Pages (from-to)189-197
Number of pages9
JournalBioelectromagnetics
Volume30
Issue number3
DOIs
StatePublished - Apr 2009
Externally publishedYes

Fingerprint

Electromagnetic Fields
Human Umbilical Vein Endothelial Cells
Osteoblasts
Vascular Endothelial Growth Factor A
Cell Proliferation
Endothelial Cells
Conditioned Culture Medium
Paracrine Communication
Mitogens
Thymidine
Enzyme-Linked Immunosorbent Assay
Bone and Bones

Keywords

  • Bone fracture
  • Co-culture
  • Endothelial cells
  • Mitogen

ASJC Scopus subject areas

  • Biophysics
  • Radiology Nuclear Medicine and imaging
  • Physiology

Cite this

Osteoblasts stimulated with pulsed electromagnetic fields increase HUVEC proliferation via a VEGF-A independent mechanism. / Hopper, Richard A.; Verhalen, Jon P.; Tepper, Oren M.; Mehrara, Babek J.; Detch, Robert; Chang, Edward I.; Baharestani, Samuel; Simon, Bruce J.; Gurtner, Geoffrey C.

In: Bioelectromagnetics, Vol. 30, No. 3, 04.2009, p. 189-197.

Research output: Contribution to journalArticle

Hopper, RA, Verhalen, JP, Tepper, OM, Mehrara, BJ, Detch, R, Chang, EI, Baharestani, S, Simon, BJ & Gurtner, GC 2009, 'Osteoblasts stimulated with pulsed electromagnetic fields increase HUVEC proliferation via a VEGF-A independent mechanism', Bioelectromagnetics, vol. 30, no. 3, pp. 189-197. https://doi.org/10.1002/bem.20459
Hopper, Richard A. ; Verhalen, Jon P. ; Tepper, Oren M. ; Mehrara, Babek J. ; Detch, Robert ; Chang, Edward I. ; Baharestani, Samuel ; Simon, Bruce J. ; Gurtner, Geoffrey C. / Osteoblasts stimulated with pulsed electromagnetic fields increase HUVEC proliferation via a VEGF-A independent mechanism. In: Bioelectromagnetics. 2009 ; Vol. 30, No. 3. pp. 189-197.
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AB - The clinically beneficial effect of low frequency pulsed electromagnetic fields (ELF-PEMF) on bone healing has been described, but the exact mechanism of action remains unclear. A recent study suggests that there is a direct autocrine mitogenic effect of ELF-PEMF on angiogenesis. The hypothesis of this study is that ELF-PEMF also has an indirect effect on angiogenesis by manipulation of vascular endothelial growth factor (VEGF)-A-based paracrine intercellular communication with neighboring osteoblasts. Conditioned media experiments measured fetal rat calvarial cell (FRC) and human umbilical vein endothelial cell (HUVEC) proliferation using tritiated thymidine uptake. We demonstrate that ELF-PEMF (15 Hz, 1.8 mT, for 8 h) has an indirect effect on the proliferation rate of both endothelial cells and osteoblasts in vitro by altering paracrine mediators. Conditioned media from osteoblast cells stimulated with ELF-PEMF increased endothelial proliferation 54-fold, whereas media from endothelial cells stimulated with ELF-PEMF did not affect osteoblast proliferation. We examined the role of the pro-angiogenic mediator VEGF-A in the mitogenic effect of ELF-PEMF- stimulated osteoblast media on endothelial cells. The production of VEGF-A by FRC as measured by ELISA was not changed by exposure to PEMF, and blocking experiments demonstrated that the ELF-PEMF-induced osteoblast-derived endothelial mitogen observed in these studies was not VEGF- A, but some other soluble angiogenic mediator. Bioelectromagnetics 30:189-197, 2009.

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