Efficacy of pulsed electromagnetic fields and electromagnetic fields tuned to the ion cyclotron resonance frequency of Ca²⁺on chondrogenic differentiation

Abstract

Previous studies provide strong evidence for the therapeutic effect of electromagnetic fields (EMFs) on different tissues including cartilage. Diverse exposure parameters applied in scientific reports and the unknown interacting mechanism of EMF with biological systems make EMF studies challenging. In 1985, Liboff proposed that when magnetic fields are tuned to the cyclotron resonance frequencies of critical ions, the motion of ions through cell membranes is enhanced, and thus biological effects appear. Such exposure system consists of a weak alternating magnetic field (B1) in the presence of a static magnetic field (B0) and depends on the relationship between the magnitudes of B0 and B1 and the angular frequency Ω. The purpose of the present study is to determine the chondrogenic potential of EMF with regards to pulsed EMF (PEMF) and the ion cyclotron resonance (ICR) theory. We used different stimulating systems to generate EMFs in which cells are either stimulated with ubiquitous PEMF parameters, frequently reported, or parameters tuned to satisfy the ICR for Ca2+ (including negative and positive control groups). Chondrogenesis was analysed after 3 weeks of treatment. Cell stimulation under the ICR condition showed positive results in the context of glycosaminoglycans and type II collagen synthesis. In contrast, the other electromagnetically stimulated groups showed no changes compared with the control groups. Furthermore, gene expression assays revealed an increase in the expression of chondrogenic markers (COL2A1, SOX9, and ACAN) in the ICR group. These results suggest that the Ca2+ ICR condition can be an effective factor in inducing chondrogenesis.

Hydrogel-hydroxyapatite-monomeric collagen type-I scaffold with low-frequency electromagnetic field treatment enhances osteochondral repair in rabbits

“…The stimulation of PEMF could increase intracellular calcium concentration by regulating calcium channels, which are required for the chondrogenic differentiation of MSCs [ 31 ]. When the parameters of EMF were tuned to the cyclotron resonance frequencies of calcium ions, Kavand et al reported an enhanced efficacy of chondrogenesis [ 33 ]. Recently, one study showed that the MSC-derived conditioned medium post EMF exposure was also capable to promote cartilage regeneration and demonstrated that EMF could regulate the paracrine function of MSCs [ 36 ].…”

“…Remarkably, increasing evidence has demonstrated that physical stimuli such as electromagnetic fields (EMF) could promote chondrogenic differentiation of BMSCs [ 31 ]. The EMF exposure induced chondrocyte proliferation and differentiation, and ECM synthesis by variable potential mechanisms, including regulating calcium channel in cell membrane [ 32 , 33 ], increasing transforming growth factor beta (TGFβ) and bone morphogenetic protein 2 (BMP2) expressions [ 34 , 35 ], and modulating MSCs secretome and paracrine function [ 36 ]. Stefani et al [ 37 ] reported that EMF stimulation improved repair and integration of engineered constructs in an animal model.…”

Hydrogel-Hydroxyapatite-Monomeric Collagen Type-I Scaffold with Low-Frequency Electromagnetic field Treatment Enhances Osteochondral Repair in Rabbits

“…The stimulation of PEMF could increase intracellular calcium concentration by regulating calcium channels, which are required for the chondrogenic differentiation of MSCs [31]. When the parameters of EMF were tuned to the cyclotron resonance frequencies of calcium ions, Kavand et al reported an enhanced e cacy of chondrogenesis [33]. Recently, one study showed that the MSC-derived conditioned medium post EMF exposure was also [71].…”

“…Remarkably, increasing evidence has demonstrated that physical stimuli such as electromagnetic elds (EMFs) could promote chondrogenic differentiation of BMSCs [31].The EMF exposure induced chondrocyte proliferation and differentiation, and ECM synthesis by variable potential mechanisms, including regulating calcium channel in cell membrane [32,33], increasing transforming growth factor beta (TGFβ) and bone morphogenetic protein 2 (BMP2) expressions [34,35], and modulating MSCs secretome and paracrine function [36]. Stefani et al [37] reported that EMF stimulation improved repair and integration of engineered constructs in an animal model.…”

Rotating magnetic field delays human umbilical vein endothelial cell aging and prolongs the lifespan of Caenorhabditis elegans

“…Under conditions of endoplasmic reticulum stress, Ca 2+ is released into the cytoplasm, resulting in increased intracellular Ca 2+ concentration. It has been reported that the endoplasmic reticulum “perceives” magnetic information by the magnetic spin dynamics of the Ca 2+ protein channel reaction induced by eddy currents [23, 24]. Identification of inhibitory osteoblasts exhibiting magnetic induction behavior within the endoplasmic reticulum represent the first practical experimental evidence that Ca 2+ is required for magnetic induction pathways in bone development [25, 26].…”