Reactive oxygen species (ROS) ubiquitously exist in mammalian cells to participate in various cellular signaling pathways. The intracellular ROS levels are dependent on the dynamic balance between ROS generation and elimination. In this review, we summarize reported studies about the influences of magnetic fields (MFs) on ROS levels. Although in most cases, MFs increased ROS levels in human, mouse, rat cells, and tissues, there are also studies showing that ROS levels were decreased or not affected by MFs. Multiple factors could cause these discrepancies, including but not limited to MF type/intensity/frequency, exposure time and assay time-point, as well as different biological samples examined. It will be necessary to investigate the influences of different MFs on ROS in various biological samples systematically and mechanistically, which will be helpful for people to get a more complete understanding about MF-induced biological effects. In addition, reviewing the roles of MFs in ROS modulation may open up new scenarios of MF application, which could be further and more widely adopted into clinical applications, particularly in diseases that ROS have documented pathophysiological roles.

Magnetic Fields and Reactive Oxygen Species

The effects of a moderate-intensity static magnetic field (SMF) on osteoporosis of the lumbar vertebrae were studied in ovariectomized rats. A small disc magnet (maximum magnetic flux density 180 mT) was implanted to the right side of spinous process of the third lumbar vertebra. Female rats in the growth stage (10 weeks old) were randomly divided into 4 groups: (i) ovariectomized and implanted with a disc magnet (SMF); (ii) ovariectomized and implanted with a nonmagnetized disc (sham); (iii) ovariectomized alone (OVX) and (vi) intact, nonoperated cage control (CTL). The blood serum 17- 𝛽 -estradiol (E 2) concentrations were measured by radioimmunoassay, and the bone mineral density (BMD) values of the femurs and the lumbar vertebrae were assessed by dual energy X-ray absorptiometry. The E 2 concentrations were statistically significantly lower for all three operated groups than those of the CTL group at the 6th week. Although there was no statistical significant difference in the E 2 concentrations between the SMF-exposed and sham-exposed groups, the BMD values of the lumbar vertebrae proximal to the SMF-exposed area statistically significantly increased in the SMF-exposed group than in the sham-exposed group. These results suggest that the SMF increased the BMD values of osteoporotic lumbar vertebrae in the ovariectomized rats.

/pdf/recovery-effects-of-a-180-mt-static-magnetic-field-on-bone-4lpc3mbaml.pdf

Recovery Effects of a 180 mT Static Magnetic Field on Bone Mineral Density of Osteoporotic Lumbar Vertebrae in Ovariectomized Rats

A functionalized TiO2/Mg2TiO4 nano-layer on biodegradable magnesium implant enables superior bone-implant integration and bacterial disinfection

VEGF-, phosphoinositide 3-kinase (PI3K)- and protein kinase C (PKC)-regulated signaling in cardiac and vascular differentiation was investigated in mouse ES cells and in ES cell-derived Flk-1+ cardiovascular progenitor cells. Inhibition of PI3K by wortmannin and LY294002, disruption of PI3K catalytic subunits p110α and p110δ using short hairpin RNA (shRNA), or inhibition of p110α with compound 15e and of p110δ with IC-87114 impaired cardiac and vascular differentiation. By contrast, TGX-221, an inhibitor of p110β, and shRNA knockdown of p110β were without significant effects. Antagonists of the PKC family, i.e. bisindolylmaleimide-1 (BIM-1), GO 6976 (targeting PKCα/βII) and rottlerin (targeting PKCδ) abolished vasculogenesis, but not cardiomyogenesis. Inhibition of Akt blunted cardiac as well as vascular differentiation. VEGF induced phosphorylation of PKCα/βII and PKCδ but not PKCζ. This was abolished by PI3K inhibitors and the VEGFR-2 antagonist SU5614. Furthermore, phosphorylation of Akt and phosphoinositide-dependent kinase-1 (PDK1) was blunted upon inhibition of PI3K, but not upon inhibition of PKC by BIM-1, suggesting that activation of Akt and PDK1 by VEGF required PI3K but not PKC. In summary, we demonstrate that PI3K catalytic subunits p110α and p110δ are central to cardiovasculogenesis of ES cells. Akt downstream of PI3K is involved in both cardiomyogenesis and vasculogenesis, whereas PKC is involved only in vasculogenesis.

/pdf/vegf-mediated-pi3k-class-ia-and-pkc-signaling-in-2rq6to4wt3.pdf

VEGF-mediated PI3K class IA and PKC signaling in cardiomyogenesis and vasculogenesis of mouse embryonic stem cells

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of synovium (synovitis), with inflammatory/immune cells and resident fibroblast-like synoviocytes (FLS) acting as major players in the pathogenesis of this disease. The resulting inflammatory response poses considerable risks as loss of bone and cartilage progresses, destroying the joint surface, causing joint damage, joint failure, articular dysfunction, and pre-mature death if left untreated. At the cellular level, early changes in RA synovium include inflammatory cell infiltration, synovial hyperplasia, and stimulation of angiogenesis to the site of injury. Different angiogenic factors promote this disease, making the role of anti-angiogenic therapy a focus of RA treatment. To control angiogenesis, mesenchymal stromal cells/pericytes (MSCs) in synovial tissue play a vital role in tissue repair. While recent evidence reports that MSCs found in joint tissues can differentiate to repair damaged tissue, this repair function can be repressed by the inflammatory milieu. Extremely-low frequency pulsed electromagnetic field (PEMF), a biophysical form of stimulation, has an anti-inflammatory effect by causing differentiation of MSCs. PEMF has also been reported to increase the functional activity of MSCs to improve differentiation to chondrocytes and osteocytes. Moreover, PEMF has been demonstrated to accelerate cell differentiation, increase deposition of collagen, and potentially return vascular dysfunction back to homeostasis. The aim of this report is to review the effects of PEMF on MSC modulation of cytokines, growth factors, and angiogenesis, and describe its effect on MSC regeneration of synovial tissue to further understand its potential role in the treatment of RA.

/pdf/targeting-mesenchymal-stromal-cells-pericytes-mscs-with-30a5l1moic.pdf

Targeting Mesenchymal Stromal Cells/Pericytes (MSCs) With Pulsed Electromagnetic Field (PEMF) Has the Potential to Treat Rheumatoid Arthritis

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.

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.

Khaled M. Omar

Papers

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.

Implementation of waste silicate glass into composition of ordinary cement for radiation shielding applications

Differential effects of high and low strength magnetic fields on mouse embryonic development and vasculogenesis of embryonic stem cells.