Adenosine Receptors as a Biological Pathway for the Anti-Inflammatory and Beneficial Effects of Low Frequency Low Energy Pulsed Electromagnetic Fields

Abstract

Several studies explored the biological effects of low frequency low energy pulsed electromagnetic fields (PEMFs) on human body reporting different functional changes. Much research activity has focused on the mechanisms of interaction between PEMFs and membrane receptors such as the involvement of adenosine receptors (ARs). In particular, PEMF exposure mediates a significant upregulation of A2A and A3ARs expressed in various cells or tissues involving a reduction in most of the proinflammatory cytokines. Of particular interest is the observation that PEMFs, acting as modulators of adenosine, are able to increase the functionality of the endogenous agonist. By reviewing the scientific literature on joint cells, a double role for PEMFs could be hypothesized in vitro by stimulating cell proliferation, colonization of the scaffold, and production of tissue matrix. Another effect could be obtained in vivo after surgical implantation of the construct by favoring the anabolic activities of the implanted cells and surrounding tissues and protecting the construct from the catabolic effects of the inflammatory status. Moreover, a protective involvement of PEMFs on hypoxia damage in neuron-like cells and an anti-inflammatory effect in microglial cells have suggested the hypothesis of a positive impact of this noninvasive biophysical stimulus.

Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration

“…PEMF stimulation has been previously shown by others to exert anti-inflammatory effects by activating adenosine receptors [41,44], while modulating intracellular calcium and activating the mechanotransduction FAK/Rho GTPases signaling pathways to induce MSC migration [67]. PEMF exposure was also shown to activate a calcium-mitochondrial axis stimulating mitochondrial respiration and promoting both mitochondriogenesis and myogenesis as well as reducing basal apoptosis and increasing telomere length via a process of adaptive magnetic mitohormesis [35].…”

“…Moreover, the expression and paracrine action of these growth factors was also demonstrated in electrically driven MSC chondrogenesis [39]. PEMF exposure has also been shown to exert anti-inflammatory effects by upregulating A2A and A3ARs, thereby mitigating the expression of pro-inflammatory cytokines [40,41]. This is supported by studies showing PEMF inhibition of the PGE2 and cycloxigenase-2 (COX-2) pathways, reducing the expression of pro-inflammatory cytokines (IL-6, IL-8) while augmenting anti-inflammatory factors (cAMP, IL-10) in synovial fibroblasts from bovine and osteoarthritic patients [42][43][44].…”

Adenosine-Related Mechanisms in Non-Adenosine Receptor Drugs

“…Refractory seizure activity can be treated with a ketogenic diet, which works in part by increasing A1AR-mediated inhibition of seizure activity (Masino et al, 2011) Electroconvulsive therapy as a treatment for mood disorders has been reported to act through the release of ATP to indirectly raise adenosine concentrations and activate the brain A1AR leading to its antidepressant effect (van Calker and Biber, 2005). Curiously, pulsating electromagnetic fields (PEMFs) were found to upregulate adenosinergic signaling in cancer and inflammation models (Varani et al, 2017;Vincenzi et al, 2018).…”

The cellular effects of Pulsed Electromagnetic Fields on osteoblasts: A review

“…Vincenzi et al [] showed that 75 Hz 2.5 mT PEMFs upregulated the expression of A 2a and A 3 AR adenosine receptors in hFOB 1.19 osteoblastic cells, as well as in other cell models, as summarized by their review [Varani et al, ]. These authors observed that PEMFs significantly increased the density and functionality of adenosine receptors while leaving their ligand affinity unchanged.…”