Static electromagnetic fields induce vasculogenesis and chondro-osteogenesis of mouse embryonic stem cells by reactive oxygen species-mediated up-regulation of vascular endothelial growth factor.
Electromagnetic fields (EMFs) are used to treat bone diseases. Herein, the effects of static EMFs on chondroosteogenesis and vasculogenesis of embryonic stem (ES) cells and bone mineralization of mouse fetuses were investigated. Treatment of differentiating ES cells with static EMFs (0.4-2 mT) stimulated vasculogenesis and chondro-osteogenesis and increased reactive oxygen species (ROS), which was abolished by the free radical scavengers trolox, 1,10-phenanthroline (phen), and the NAD(P)H oxidase inhibitor diphenylen iodonium (DPI). In contrast, EMFs of 10 mT field strength exerted inhibitory effects on vasculogenesis and chondro-osteogenesis despite robust ROS generation. EMFs of 1 mT and 10 mT increased and decreased vascular endothelial growth factor (VEGF) expression, respectively, which was abolished by DPI and radical scavengers. EMFs activated extracellular-regulated kinase 1/2 (ERK1/2), p38, and c-jun N-terminal kinase (JNK), which was sensitive to DPI treatment. The increase in VEGF by EMFs was inhibited by the ERK1/2 inhibitor U0126 but not by SB203580 and SP600125, which are p38 and JNK inhibitors, respectively, suggesting VEGF regulation by ERK1/2. Chondroosteogenesis and vasculogenesis of ES cells was blunted by trolox, DPI, and the VEGF receptor-2 (flk-1) antagonist SU5614. In mouse fetuses 1 mT EMFs increased and 10 mT EMFs decreased bone mineralization, which was abolished in the presence of trolox. Hence, EMFs induced chondro-osteogenesis and vasculogenesis in ES cells and bone mineralization of mouse fetuses by a ROS-dependent up-regulation of VEGF expression.
Department of Internal Medicine I, Cardiology Division, Friedrich Schiller University Jena, Germany.
Mohamed M
MM
Bekhite
Andreas
A
Finkensieper
Fouad A
FA
Abou-Zaid
Ibrahim K
IK
El-Shourbagy
Khaled M
KM
Omar
Hans-Reiner
HR
Figulla
Heinrich
H
Sauer
Maria
M
Wartenberg
D000818:Animals; D002113:Calcification, Physiologic; D004574:Electromagnetic Fields; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology*; D005333:Fetus; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018919:Neovascularization, Physiologic; D010012:Osteogenesis; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000187:drug effects / Q000502:physiology
D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D020928:Mitogen-Activated Protein Kinases