Life Rhythm as a Symphony of Oscillatory Patterns: Electromagnetic Energy and Sound Vibration Modulates Gene Expression for Biological Signaling and Healing

Note: this article is very lengthy, but has many references to other pertinent papers:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010966/

Of particular interest to cell-cell communication with regard to EMF sensitivity is the messenger molecule nitric oxide (NO). NO diffuses freely and rapidly across cell membranes, plays key roles in the rapid regulation of microcirculation, inflammation, and the cell growth and repair process,118 and has been demonstrated to regulate chromatin folding dynamics, and thus gene expression, in human endothelial cells.119 The importance of transient NO signaling is underscored by the observation that Nature has evolved a remarkable sensitivity to subcellular, subsecond (100 ms) NO transients in the low picomolar range, as demonstrated in human embryonic kidney HEK 293T cell lines.120 A growing body of literature has demonstrated that NO signaling plays a significant role in biological EMF transduction, and effects on NO expression and NO-dependent pathways have been reported for a wide variety of nonthermal EMF amplitudes, frequencies, and signal shapes.121–137 Thus, modulation of NO signaling has been established as one means by which cells and tissues can respond rapidly to changes in the EMF environment and could interact with nuclear DNA through modulation of chromosome folding dynamics.119

Even within this narrow category, a large number of effects have been observed over a wide range of nonthermal EMF amplitudes, frequencies and waveform shapes, and the current rate of progress is rapidly increasing. Recent reports of such effects are displayed in the following list.

• Decreased proliferation, upregulation of neuronal differentiation marker (MAP2)157
• A decrease in filament protein Nestin in bone marrow derived mesenchymal stem cells157
• Increased filament protein NF-L, MAP2 and NeuroD1 in human bone marrow derived mesenchymal stem cells158,159
• Induction of rat bone mesenchymal stromal cells to differentiate into functional neurons160
• Significant up-regulation of early and late neuronal differentiation markers and significant down-regulation of the transforming growth factor-α (TGF-α) and the fibroblast growth factor-4 (FGF-4) in NT2 pluripotent human testicular embryonal carcinoma cells161
• Increased osteogenic gene expression, alkaline phosphate activity in adipose-derived stem cells162
• Enhanced chondrogenic gene expression (SOX-9, collagen type II, and aggrecan) in adipose-derived stem cells163
• Modulation of early (such as Runx-2 and osterix) and late (specifically, osteopontin and osteocalcin) osteogenic genes in adult human mesenchymal stem cells164
• Up-regulation of insulin factor genes, peroxisome proliferative activity, calcium channel gene, genes for mitochondrial ribosomal protein S, and uncoupling protein 2, down-regulation of tumor necrosis factor alpha and interleukin 6 in human embryonic stem cells165
• Enhanced expression of the collagen I gene in mouse bone marrow stromal cells166
• Increase in genetic markers for differentiation in human osteoprogenitor cells167
• Increased expression of Osterix and IGF-1 genes in rat bone marrow mesenchymal stem cells168
• Increased expression of osteogenic regulatory gene cbfa1 in human bone marrow mesenchymal stem cells169
• Up-regulation of cardiac markers such as troponin I and myosin heavy chain, decrease in angiogenic markers such as vascular endothelial growth factor and kinase domain receptor in cardiac stem cells170
• Up-regulation of expressions of Bmp1, Bmp7 mRNA and down-regulation of Egf, Egfr in murine bone marrow mesenchymal stem cells171
• Altered gene expression in human mesenchymal stem cells and chondrocytes172
• Alterations in transcript levels of the apoptosis-related bcl-2, bax, and cell cycle regulatory GADD45 genes in embryonic stem cell-derived neural progenitor cells173
• Up-regulation of c-jun, p21 and egr-1 mRNA gene expression levels in pluripotent embryonic stem cells174
• Alterations in gene expression through an EMF-activated free radical mechanism and175
• Increased expression of p21(WAF1/CIP1), cdk5 and cyp19 genes, involved in neuronal differentiation176
• Increased ALP gene expression and other osteogenic markers in bone marrow-derived human mesenchymal stem cells175
• Enhanced expression of ACTN2, alpha-actin and TNNT2 in rat bone marrow-derived mesenchymal stem cells178
• Induction of differentiation of mesenchymal stem cells into cardiomyocyte-like cells179
• Differentiation of rat bone marrow-derived mesenchymal stem cells into chondrocyte-like cells180
• Increased expression of GATA-4 and Nkx-2.5 cardiac lineage-promoting genes in embryonic stem cells181

Effect of pulsed electromagnetic field treatment on programmed resolution of inflammation pathway markers in human cells in culture

Abstract

Inflammation is a complex process involving distinct but overlapping biochemical and molecular events that are highly regulated. Pulsed electromagnetic field (PEMF) therapy is increasingly used to treat pain and edema associated with inflammation following surgery involving soft tissue. However, the molecular and cellular effects of PEMF therapy on pathways involved in the resolution of inflammation are poorly understood. Using cell culture lines relevant to trauma-induced inflammation of the skin (human dermal fibroblasts, human epidermal keratinocytes, and human mononuclear cells), we investigated the effect of PEMF on gene expression involved in the acute and resolution phases of inflammation. We found that PEMF treatment was followed by changes in the relative amount of messenger (m)RNAs encoding enzymes involved in heme catabolism and removal of reactive oxygen species, including an increase in heme oxygenase 1 and superoxide dismutase 3 mRNAs, in all cell types examined 2 hours after PEMF treatment. A relative increase in mRNAs encoding enzymes involved in lipid mediator biosynthesis was also observed, including an increase in arachidonate 12- and 15-lipoxygenase mRNAs in dermal fibroblasts and epidermal keratinocytes, respectively. The relative amount of both of these lipoxygenase mRNAs was elevated in mononuclear cells following PEMF treatment relative to nontreated cells. PEMF treatment was also followed by changes in the mRNA levels of several cytokines. A decrease in the relative amount of interleukin 1 beta mRNA was observed in mononuclear cells, similar to that previously reported for epidermal keratinocytes and dermal fibroblasts. Based on our results, we propose a model in which PEMF therapy may promote chronic inflammation resolution by mediating gene expression changes important for inhibiting and resolving inflammation.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346366/