title: Osteoblasts stimulated with pulsed electromagnetic fields increase HUVEC proliferation via a VEGF-A independent mechanism.
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.
authors.affiliation: Department of Surgery, University of Washington, Seattle, WA 98105, USA. richard.hopper@seattlechildrens.org
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hopper
authors.forename: Jon P
authors.initials: JP
authors.lastname: VerHalen
authors.forename: Oren
authors.initials: O
authors.lastname: Tepper
authors.forename: Babek J
authors.initials: BJ
authors.lastname: Mehrara
authors.forename: Robert
authors.initials: R
authors.lastname: Detch
authors.forename: Edward I
authors.initials: EI
authors.lastname: Chang
authors.forename: Samuel
authors.initials: S
authors.lastname: Baharestani
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Simon
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Gurtner
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology / Q000528:radiation effects; D004574:Electromagnetic Fields; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D051381:Rats; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
chemical_list: D017077:Culture Media, Conditioned; D042461:Vascular Endothelial Growth Factor A