Pulsed Electromagnetic Fields Exposure Research Articles

Directionalities of magnetic fields and topographic scaffolds synergise to enhance MSC chondrogenesis

Mesenchymal stem cell (MSC) chondrogenesis is modulated by diverse biophysical cues. We have previously shown that brief, low-amplitude pulsed electromagnetic fields (PEMFs) differentially enhance MSC chondrogenesis in scaffold-free pellet cultures versus conventional tissue culture plastic (TCP), indicating an interplay between magnetism and micromechanical environment. Here, we examined the influence of PEMF directionality over the chondrogenic differentiation of MSCs laden on electrospun fibrous scaffolds of either random (RND) or aligned (ALN) orientations. Correlating MSCs’ chondrogenic outcome to pFAK activation and YAP localisation, MSCs on the RND scaffolds experienced the least amount of resting mechanical stress and underwent greatest chondrogenic differentiation in response to brief PEMF exposure (10 min at 1 mT) perpendicular to the dominant plane of the scaffolds (Z-directed). By contrast, in MSC-impregnated RND scaffolds, greatest mitochondrial respiration resulted from X-directed PEMF exposure (parallel to the scaffold plane), and was associated with curtailed chondrogenesis. MSCs on TCP or the ALN scaffolds exhibited greater resting mechanical stress and accordingly, were unresponsive, or negatively responsive, to PEMF exposure from all directions. The efficacy of PEMF-induced MSC chondrogenesis is hence regulated in a multifaceted manner involving focal adhesion dynamics, as well as mitochondrial responses, culminating in a final cellular response. The combined contributions of micromechanical environment and magnetic field orientation hence will need to be considered when designing magnetic exposure paradigms.

Pulsed Electromagnetic Fields Stimulate HIF-1α-Independent VEGF Release in 1321N1 Human Astrocytes Protecting Neuron-Like SH-SY5Y Cells from Oxygen-Glucose Deprivation.

Pulsed electromagnetic fields (PEMFs) are emerging as an innovative, non-invasive therapeutic option in different pathological conditions of the central nervous system, including cerebral ischemia. This study aimed to investigate the mechanism of action of PEMFs in an in vitro model of human astrocytes, which play a key role in the events that occur following ischemia. 1321N1 cells were exposed to PEMFs or hypoxic conditions and the release of relevant neurotrophic and angiogenic factors, such as VEGF, EPO, and TGF-β1, was evaluated by means of ELISA or AlphaLISA assays. The involvement of the transcription factor HIF-1α was studied by using the specific inhibitor chetomin and its expression was measured by flow cytometry. PEMF exposure induced a time-dependent, HIF-1α-independent release of VEGF from 1321N1 cells. Astrocyte conditioned medium derived from PEMF-exposed astrocytes significantly reduced the oxygen-glucose deprivation-induced cell proliferation and viability decrease in the neuron-like cells SH-SY5Y. These findings contribute to our understanding of PEMFs action in neuropathological conditions and further corroborate their therapeutic potential in cerebral ischemia.

Directionalities of Magnetic Fields and Topographic Scaffolds Synergise to Enhance MSC Chondrogenesis

Mesenchymal stem cell (MSC)-based chondrogenesis is modulated by diverse biophysical cues. We have previously shown that brief, low-amplitude pulsed electromagnetic fields (PEMFs) differentially enhance MSC chondrogenesis in scaffold-free pellet cultures versus conventional tissue culture plastic (TCP), indicating an interplay between magnetism and micromechanical environment. Here, we examined the influence of PEMF directionality over the chondrogenic differentiation of MSCs laden onto electrospun fibrous scaffolds of either random (RND) or aligned (ALN) orientations. Interactions were detected between magnetic field orientation with that of the cells that combined with micromechanical environment at the level of mitochondrial respiration. Based on pFAK staining and YAP localisation, MSCs on the RND scaffolds were shown to be experiencing the least amount of resting mechanical stress and were found to undergo robust chondrogenic differentiation in response to PEMF exposure perpendicular to the dominant plane of the scaffolds (Z-directed) for only ten minutes at an amplitude of 1 mT. By contrast, MSCs plated onto TCP or the ALN scaffolds gave indications of greater resting mechanical stress accordingly, were unresponsive, or responded negatively, to Z-directed PEMFs. Such interactions agree with a mitohormetic mechanism of cumulative interaction between magnetic fields and the mechanical environment. Moreover, PEMFs demonstrated a strong interaction with MSC alignment, whereby Y-directed magnetic fields applied parallel to the long-axis of MSCs on Y-ALN scaffolds exhibited reduced chondrogenesis. These results indicate that diverse biophysical parameters interact with magnetic fields to culminate in a final cell response that will need to be taken into consideration when designing an effective magnetic exposure paradigm.

A2A adenosine receptors are involved in the reparative response of tendon cells to pulsed electromagnetic fields.

Tendinopathy is a degenerative disease in which inflammatory mediators have been found to be sometimes present. The interaction between inflammation and matrix remodeling in human tendon cells (TCs) is supported by the secretion of cytokines such as IL-1β, IL-6 and IL-33. In this context, it has been demonstrated that pulsed electromagnetic fields (PEMFs) were able to reduce inflammation and promote tendon marker synthesis. The aim of this study was to evaluate the anabolic and anti-inflammatory PEMF-mediated response on TCs in an in vitro model of inflammation. Moreover, since PEMFs enhance the anti-inflammatory efficacy of adenosine through the adenosine receptors (ARs), the study also focused on the role of A2AARs. Human TCs were exposed to PEMFs for 48 hours. After stimulation, A2AAR saturation binding experiments were performed. Along with 48 hours PEMF stimulation, TCs were treated with IL-1β and A2AAR agonist CGS-21680. IL-1Ra, IL-6, IL-8, IL-10, IL-33, VEGF, TGF-β1, PGE2 release and SCX, COL1A1, COL3A1, ADORA2A expression were quantified. PEMFs exerted A2AAR modulation on TCs and promoted COL3A1 upregulation and IL-33 secretion. In presence of IL-1β, TCs showed an upregulation of ADORA2A, SCX and COL3A1 expression and an increase of IL-6, IL-8, PGE2 and VEGF secretion. After PEMF and IL-1β exposure, IL-33 was upregulated, whereas IL-6, PGE2 and ADORA2A were downregulated. These findings demonstrated that A2AARs have a role in the promotion of the TC anabolic/reparative response to PEMFs and to IL-1β.

Cell-Derived Vesicles as TRPC1 Channel Delivery Systems for the Recovery of Cellular Respiratory and Proliferative Capacities.

Pulsed electromagnetic fields (PEMFs) are capable of specifically activating a TRPC1-mitochondrial axis underlying cell expansion and mitohormetic survival adaptations. This study characterizes cell-derived vesicles (CDVs) generated from C2C12 murine myoblasts and shows that they are equipped with the sufficient molecular machinery to confer mitochondrial respiratory capacity and associated proliferative responses upon their fusion with recipient cells. CDVs derived from wild type C2C12 myoblasts include the cation-permeable transient receptor potential (TRP) channels, TRPC1 and TRPA1, and directly respond to PEMF exposure with TRPC1-mediated calcium entry. By contrast, CDVs derived from C2C12 muscle cells in which TRPC1 has been genetically knocked-down using CRISPR/Cas9 genome editing, do not. Wild type C2C12-derived CDVs are also capable of restoring PEMF-induced proliferative and mitochondrial activation in two C2C12-derived TRPC1 knockdown clonal cell lines in accordance to their endogenous degree of TRPC1 suppression. C2C12 wild type CDVs respond to menthol with calcium entry and accumulation, likewise verifying TRPA1 functional gating and further corroborating compartmental integrity. Proteomic and lipidomic analyses confirm the surface membrane origin of the CDVs providing an initial indication of the minimal cellular machinery required to recover mitochondrial function. CDVs hence possess the potential of restoring respiratory and proliferative capacities to senescent cells and tissues.

Pulsed electromagnetic fields improve the healing process of Achilles tendinopathy: a pilot study in a rat model.

AimsIn the context of tendon degenerative disorders, the need for innovative conservative treatments that can improve the intrinsic healing potential of tendon tissue is progressively increasing. In this study, the role of pulsed electromagnetic fields (PEMFs) in improving the tendon healing process was evaluated in a rat model of collagenase-induced Achilles tendinopathy.MethodsA total of 68 Sprague Dawley rats received a single injection of type I collagenase in Achilles tendons to induce the tendinopathy and then were daily exposed to PEMFs (1.5 mT and 75 Hz) for up to 14 days - starting 1, 7, or 15 days after the injection - to identify the best treatment option with respect to the phase of the disease. Then, 7 and 14 days of PEMF exposure were compared to identify the most effective protocol.ResultsThe daily exposure to PEMFs generally provided an improvement in the fibre organization, a decrease in cell density, vascularity, and fat deposition, and a restoration of the physiological cell morphology compared to untreated tendons. These improvements were more evident when the tendons were exposed to PEMFs during the mid-acute phase of the pathology (7 days after induction) rather than during the early (1 day after induction) or the late acute phase (15 days after induction). Moreover, the exposure to PEMFs for 14 days during the mid-acute phase was more effective than for 7 days.ConclusionPEMFs exerted a positive role in the tendon healing process, thus representing a promising conservative treatment for tendinopathy, although further investigations regarding the clinical evaluation are needed.Cite this article: Bone Joint Res 2020;9(9):613–622.

Pulsed Electromagnetic Fields Modulate miRNAs During Osteogenic Differentiation of Bone Mesenchymal Stem Cells: a Possible Role in the Osteogenic-angiogenic Coupling.

Despite the high intrinsic ability of bone tissue to regenerate, bone healing fails in some pathological conditions and especially in the presence of large defects. Due to the strong relationship between bone development and vascularization during in vivo bone formation and repair, strategies promoting the osteogenic-angiogenic coupling are crucial for regenerative medicine. Increasing evidence shows that miRNAs play important roles in controlling osteogenesis and bone vascularization and are important tool in medical research although their clinical use still needs to optimize miRNA stability and delivery. Pulsed electromagnetic fields (PEMFs) have been successfully used to enhance bone repair and their clinical activity has been associated to their ability to promote the osteogenic differentiation of human mesenchymal stem cells (hMSCs). In this study we investigated the potential ability of PEMF exposure to modulate selected miRNAs involved in the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs). We show that, during in vitro hBMSC differentiation, PEMFs up-modulate the expression of miR-26a and miR-29b, which favor osteogenic differentiation, and decrease miR-125b which acts as an inhibitor miRNA. As PEMFs promote the expression and release of miRNAs also involved in angiogenesis, we conclude that PEMFs may represent a noninvasive and safe strategy to modulate miRNAs with relevant roles in bone repair and with the potential to regulate the osteogenic-angiogenic coupling.

In Vitro Production of Calcified Bone Matrix onto Wool Keratin Scaffolds via Osteogenic Factors and Electromagnetic Stimulus.

Pulsed electromagnetic field (PEMF) has drawn attention as a potential tool to improve the ability of bone biomaterials to integrate into the surrounding tissue. We investigated the effects of PEMF (frequency, 75 Hz; magnetic induction amplitude, 2 mT; pulse duration, 1.3 ms) on human osteoblast-like cells (SAOS-2) seeded onto wool keratin scaffolds in terms of proliferation, differentiation, and production of the calcified bone extracellular matrix. The wool keratin scaffold offered a 3D porous architecture for cell guesting and nutrient diffusion, suggesting its possible use as a filler to repair bone defects. Here, the combined approach of applying a daily PEMF exposure with additional osteogenic factors stimulated the cells to increase both the deposition of bone-related proteins and calcified matrix onto the wool keratin scaffolds. Also, the presence of SAOS-2 cells, or PEMF, or osteogenic factors did not influence the compression behavior or the resilience of keratin scaffolds in wet conditions. Besides, ageing tests revealed that wool keratin scaffolds were very stable and showed a lower degradation rate compared to commercial collagen sponges. It is for these reasons that this tissue engineering strategy, which improves the osteointegration properties of the wool keratin scaffold, may have a promising application for long term support of bone formation in vivo.

Single pulsed electromagnetic field restores bone mass and microarchitecture in denervation/disuse osteopenic mice

Pulsed electromagnetic fields (PEMFs) have been proposed to treat bone loss. However, time-consuming is the main complaint. A time-saving and effective treatment is of expectation. Previously, we showed a 3 min daily of single pulsed electromagnetic field (SPEMF) accelerated bone formation of long bone defect in mice. Here we compared the effect of SPEMF with PEMF for treating denervation/disuse osteopenic mice.Healthy mice were divided into 3 groups: intact mice (INT), INT + PEMF, and INT + SPEMF. Induced osteopenic mice were divided to osteopenia (IOP), IOP + PEMF, and IOP + SPEMF groups. The PEMF treated groups were subjected to daily 8 h PEMF(15 Hz, 18 G) exposure, while SPEMF treated groups were daily 3 min SPEMF(0.2 Hz, 1 T) exposure. BMD was evaluated every two weeks during the 12 weeks of treatment. Microarchitecture was evaluated on week 12.SPEMF significantly reversed bone loss in IOP mice as early as 6 weeks post-treatment, while PEMF reversed bone loss after 8 weeks. Bone volume was significantly increased in the IOP + PEMF and IOP + SPEMF group. Besides, bone volume and trabecular number of IOP + SPEMF mice were restored to the levels of INT mice in 12 weeks. Our finding suggests SPEMF increased BMD and restored microarchitecture of disuse osteopenic mice to healthy level.

Pulsed Electromagnetic Field Stimulation of Bone Healing and Joint Preservation: Cellular Mechanisms of Skeletal Response

The US FDA has approved pulsed electromagnetic fields (PEMFs) as a safe and effective treatment for nonunions of bone. Despite its clinical use, the mechanisms of action of electromagnetic stimulation of the skeleton have been elusive. Recently, cell membrane receptors have been identified as the site of action of PEMF and provide a mechanistic rationale for clinical use. This review highlights key processes in cell responses to PEMF as follows: (1) signal transduction through A2A and A3 adenosine cell membrane receptors and (2) dose-response effects on the synthesis of structural and signaling extracellular matrix (ECM) components. Through these actions, PEMF can increase the structural integrity of bone and cartilage ECM, enhancing repair, and alter the homeostatic balance of signaling cytokines, producing anti-inflammatory effects. PEMFs exert a proanabolic effect on the bone and cartilage matrix and a chondroprotective effect counteracting the catabolic effects of inflammation in the joint environment. Understanding of PEMF membrane targets, and of the specific intracellular pathways involved, culminating in the synthesis of ECM proteins and reduction in inflammatory cytokines, should enhance confidence in the clinical use of PEMF and the identification of clinical conditions likely to be affected by PEMF exposure.

Pulsed Electromagnetic Field Versus Whole Body Vibration on Cartilage and Subchondral Trabecular Bone in Mice With Knee Osteoarthritis.

Pulsed electromagnetic field (PEMF) and whole body vibration (WBV) interventions are expected to be important strategies for management of osteoarthritis (OA). The aim of the study was to investigate the comparative effectiveness of PEMF versus WBV on cartilage and subchondral trabecular bone in mice with knee OA (KOA) induced by surgical destabilization of the medial meniscus (DMM). Forty 12-week-old male C57/BL mice were randomly divided into four groups (n = 10): Control, OA, PEMF, and WBV. OA was induced (OA, PEMF, and WBV groups) by surgical DMM of right knee joint. Mice in PEMF group received 1 h/day PEMF exposure with 75 Hz, 1.6 mT for 4 weeks, and the WBV group was exposed to WBV for 20 min/day with 5 Hz, 4 mm, 0.3 g peak acceleration for 4 weeks. Micro-computed tomography (micro-CT), histology, and immunohistochemistry analyses were performed to evaluate the changes in cartilage and microstructure of trabecular bone. The bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) increased, and bone surface/bone volume (BS/BV) decreased by micro-CT analysis in PEMF and WBV groups. The Osteoarthritis Research Society International (OARSI) scores in PEMF and WBV groups were significantly lower than in the OA group. Immunohistochemical results showed that PEMF and WBV promoted expressions of Aggrecan, and inhibited expressions of IL-1β, ADAMTS4, and MMP13. Superior results are seen in PEMF group compared with WBV group. Both PEMF and WBV were effective, could delay cartilage degeneration and preserve subchondral trabecular bone microarchitecture, and PEMF was found to be superior to WBV. Bioelectromagnetics. 2020;41:298-307 © 2020 Bioelectromagnetics Society.

The Effect of Pulsed Electromagnetic Field Exposure on Fracture Healing Through the Wnt Signal Pathway

Pulsed Electromagnetic Fields (PEMF) is reported to encourage the healing of nonunion fractures. However, the mechanism by which this occurs is still not known. Wnt signaling pathways are believed to be important signaling pathways in bone formation. This study will evaluate the healing of delayed union femur fracture, given PEMF exposure. 48 Spraque Dawley rats were fracturized at the left femoral shaft. These rats were randomized into two groups: A control group (24 rats) and the PEMF group (24 rats). The PEMF group was given PEMF exposure of 1.6 mT, with a frequency of 50 Hz for 4 h every day for 5, 10, 18 and 28 days, while the control group was not given PEMF exposure. Consequently, on days 5, 10, 18 and 28 days after fracture, 6 rats from each group were sacrificed. Callus bone was used for histological and RT-PCR examination on the expression of Wnt10b, Wnt5a and β-catenin. Blood samples were taken to examine Alkaline Phosphatase (ALP) activity using the ELISA method. Hematoxylin Eosin (HE) staining results showed that in the initial phase of healing, fibrous tissue in the fracture gap of the PEMF group was less compared to the control group. In the PEMF group, ALP activity increased significantly on day 10. This is thought to be related to an increase in osteoblast activity in a bone matrix formation. Furthermore, RT-PCR examination results showed that Wnt10b, Wnt5a and β-catenin gene expression was higher in the PEMF group compared to the control group. It can be concluded that PEMF exposure is thought to accelerate delayed union fracture healing through the Wnt signal pathway.

Design and Study of Novel Tunable ELF-PEMF System for Therapeutic Applications

ABSTRACTMicrobial infection is a major barrier to wound care and repair process of the cells. Various US-FDA-approved drugs and surgical procedures have been used for wound healing progression. However, the use of these pharmaceutical products has an associated toxicity and may produce harmful side effects. To overcome these problems, researchers worldwide are trying to develop non-invasive wound healing processes for wound care. We have developed a unique, tunable and Arduino microcontroller-based extremely low-frequency (ELF) pulsed electromagnetic field (PEMF) device for accelerating the wound healing process by reducing the microbial infection. The layout and detailed design of the device are presented here. Simulations carried out for the fabrication of the Helmholtz coil used in the PEMF device are also presented. This system can provide the flexibility of dose substance by selecting the type and frequency of the waveform, exposure duration, and magnetic field strength. To test the efficacy of the device in the biological system, we have designed colony-forming unit assay in Staphylococcus aureus with an exposure to PEMF in the frequency range of 5–30 Hz for 90 min. The experiments have been conducted in controlled EMF environments as per the international standard exposure guidelines. The results show a 60% reduction in S. aureus CFU after 90 minutes of PEMF exposure, and hence, show that the designed system is very effective for wound care by reducing the microbial growth.

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

BackgroundThe mesenchymal stem cell (MSC) secretome, via the combined actions of its plethora of biologically active factors, is capable of orchestrating the regenerative responses of numerous tissues by both eliciting and amplifying biological responses within recipient cells. MSCs are “environmentally responsive” to local micro-environmental cues and biophysical perturbations, influencing their differentiation as well as secretion of bioactive factors. We have previously shown that exposures of MSCs to pulsed electromagnetic fields (PEMFs) enhanced MSC chondrogenesis. Here, we investigate the influence of PEMF exposure over the paracrine activity of MSCs and its significance to cartilage regeneration.MethodsConditioned medium (CM) was generated from MSCs subjected to either 3D or 2D culturing platforms, with or without PEMF exposure. The paracrine effects of CM over chondrocytes and MSC chondrogenesis, migration and proliferation, as well as the inflammatory status and induced apoptosis in chondrocytes and MSCs was assessed.ResultsWe show that benefits of magnetic field stimulation over MSC-derived chondrogenesis can be partly ascribed to its ability to modulate the MSC secretome. MSCs cultured on either 2D or 3D platforms displayed distinct magnetic sensitivities, whereby MSCs grown in 2D or 3D platforms responded most favorably to PEMF exposure at 2 mT and 3 mT amplitudes, respectively. Ten minutes of PEMF exposure was sufficient to substantially augment the chondrogenic potential of MSC-derived CM generated from either platform. Furthermore, PEMF-induced CM was capable of enhancing the migration of chondrocytes and MSCs as well as mitigating cellular inflammation and apoptosis.ConclusionsThe findings reported here demonstrate that PEMF stimulation is capable of modulating the paracrine function of MSCs for the enhancement and re-establishment of cartilage regeneration in states of cellular stress. The PEMF-induced modulation of the MSC-derived paracrine function for directed biological responses in recipient cells or tissues has broad clinical and practical ramifications with high translational value across numerous clinical applications.

Signaling pathways involved in anti-inflammatory effects of Pulsed Electromagnetic Field in microglial cells

Literature studies suggest important protective effects of low-frequency, low-energy pulsed electromagnetic fields (PEMFs) on inflammatory pathways affecting joint and cerebral diseases. However, it is not clear on which bases they affect neuroprotection and the mechanism responsible is yet unknown. Therefore the aim of this study was to identify the molecular targets of PEMFs anti-neuroinflammatory action. The effects of PEMF exposure in cytokine production by lipopolysaccharide (LPS)-activated N9 microglial cells as well as the pathways involved, including adenylyl cyclase (AC), phospholipase C (PLC), protein kinase C epsilon (PKC-ε) and delta (PKC-δ), p38, ERK1/2, JNK1/2 mitogen activated protein kinases (MAPK), Akt and caspase 1, were investigated. In addition, the ability of PEMFs to modulate ROS generation, cell invasion and phagocytosis, was addressed. PEMFs reduced the LPS-increased production of TNF-α and IL-1β in N9 cells, through a pathway involving JNK1/2. Furthermore, they decreased the LPS-induced release of IL-6, by a mechanism not dependent on AC, PLC, PKC-ε, PKC-δ, p38, ERK1/2, JNK1/2, Akt and caspase 1. Importantly, a significant effect of PEMFs in the reduction of crucial cell functions specific of microglia like ROS generation, cell invasion and phagocytosis was found. PEMFs inhibit neuroinflammation in N9 cells through a mechanism involving, at least in part, the activation of JNK MAPK signalling pathway and may be relevant to treat a variety of diseases characterized by neuroinflammation.

Synergistic effects of polyaniline and pulsed electromagnetic field to stem cells osteogenic differentiation on polyvinylidene fluoride scaffold

Repairing the lost or damaged mandible is very difficult and time-consuming, so there is a great hope for tissue engineering to accelerate it. At the present study, electrospinning was applied to fabricate polyvinylidene fluoride (PVDF) and PVDF-polyaniline (PANI) composite scaffolds. In addition, extremely low frequency pulsed electromagnetic field (PEMF) was applied for treating the stem cells derived from dental pulp (DPSCs) when cultured on the nanofibrous scaffolds. Osteoinductive property of the fabricated PVDF, PVDF-PANI scaffold at the presence and absence of the PEMF was investigated by evaluating the common osteogenic differentiation markers in seeded-DPSCs on the scaffold. Results demonstrated that cell attachment, protein adsorption and cells viability were increased when PEMF was applied. In addition, ALP activity, calcium content, osteogenic genes and protein evaluations confirmed that PEMF could significantly increase osteoinductivity of the PVDF while composite with PANI. According to the results, the use of polymers with piezoelectricity and conductivity features plus PEMF exposure has a promising potential to improve the current treatment methods in bone and mandibular defects.

Effects of Low-Frequency Pulsed Electromagnetic Fields on High-Altitude Stress Ulcer Healing in Rats.

High-altitude stress ulcer (HSU) has constantly been a formidable clinical challenge for high-altitude and severe hypoxia. Pulsed electromagnetic fields (PEMFs) have been verified to have the ability to penetrate tissues, and the biological effects have been confirmed effective on various tissue restorations. However, the therapeutic effect of PEMFs on HSU has been rarely reported. This study aimed to evaluate the effects of PEMFs on HSU healing systematically. Sprague–Dawley rats were assigned to control, HSU, and HSU+PEMF groups. The HSU models were induced by restraint stress under low-pressure hypoxia. The HSU+PEMF group was subjected to PEMF exposure. During the HSU healing, gastric juice pH values, ulcer index (UI), and histopathologic changes were investigated. Furthermore, tumor necrosis factor-α (TNF-α) was determined to analyze the severity of gastric membrane inflammations. Norepinephrine (NE), which influences gastric acid secretion, was measured. Results indicated the UI of the HSU+PEMF decreased faster than that of the HSU group. Histopathologic observation suggested that the ulcer tissue healing is faster in the HSU+PEMF group than in the HSU group. The TNF-α/total protein results revealed that the inflammation of the HSU+PEMF group is suppressed effectively. The pH values are higher in the HSU+PEMF group than in the HSU, as confirmed by NE examination. The results indicated that low-frequency PEMFs can penetrate stomach tissues to relieve the symptoms of HSU and promote the regeneration of disturbed tissues, thus implying the clinical potential of PEMF therapy for HSU treatment.

Global Responses of Il-1β-Primed 3D Tendon Constructs to Treatment with Pulsed Electromagnetic Fields.

Tendinopathy is accompanied by a cascade of inflammatory events promoting tendon degeneration. Among various cytokines, interleukin-1β plays a central role in driving catabolic processes, ultimately resulting in the activation of matrix metalloproteinases and a diminished collagen synthesis, both of which promote tendon extracellular matrix degradation. Pulsed electromagnetic field (PEMF) therapy is often used for pain management, osteoarthritis, and delayed wound healing. In vitro PEMF treatment of tendon-derived cells was shown to modulate pro-inflammatory cytokines, potentially limiting their catabolic effects. However, our understanding of the underlying cellular and molecular mechanisms remains limited. We therefore investigated the transcriptome-wide responses of Il-1β-primed rat Achilles tendon cell-derived 3D tendon-like constructs to high-energy PEMF treatment. RNASeq analysis and gene ontology assignment revealed various biological processes to be affected by PEMF, including extracellular matrix remodeling and negative regulation of apoptosis. Further, we show that members of the cytoprotective Il-6/gp130 family and the Il-1β decoy receptor Il1r2 are positively regulated upon PEMF exposure. In conclusion, our results provide fundamental mechanistic insight into the cellular and molecular mode of action of PEMF on tendon cells and can help to optimize treatment protocols for the non-invasive therapy of tendinopathies.

Alterations of Hematologic and Hematopoietic Parameters in Mice Exposed to Pulsed Electromagnetic Field.

Effects of pulsed electromagnetic field (PEMF) on hematology and hematopoiesis might vary with different PEMF parameters. The purpose of this study was to evaluate the possible effects of PEMF exposure at different pulses on hematologic and hematopoietic parameters in mice. Groups of male BALB/c mice were whole body exposed or were sham exposed (control) to PEMF at 100, 1000, and 10000 pulses. After PEMF exposure, blood samples and bone marrow cells of mice were collected for hematologic examinations, bone marrow nucleated cell counting, colony-forming units of granulocyte-macrophage (CFU-GM) colony assay, and serum granulocyte-macrophage colony-stimulating factor (GM-CSF) assay. Compared with the control group, white blood cells (WBC) and lymphocytes (LYM) in the 100 and 1000 pulses exposed groups were significantly increased but not changed in the 10000 pulses exposed group. Red blood cells (RBC), hemoglobin (HGB), and platelets (PLT) were not changed in all exposed groups. There was no significant difference in mouse bone marrow nucleated cell number between the control group and each exposed group 7 days after PEMF exposure. The CFU-GM clone number of bone marrow cells and serum GM-CSF level were significantly increased in the 100 and 1000 pulses exposed group but not changed in the 10000 pulses exposed group. Our results indicated that the PEMF exposure at fewer pulses may induce statistically significant alterations in some hematologic and hematopoietic parameters of mice but no changes can be found in the more pulses PEMF-exposed groups.

Low‑frequency pulsed electromagnetic field inhibits RANKL‑induced osteoclastic differentiation in RAW264.7 cells by scavenging reactive oxygen species.

Bone homeostasis is a dynamic balance maintained by bone formation and resorption. An increase in the number and activity of osteoclasts leads to excessive bone resorption, which in turn results in bone disease, including osteoporosis. Therefore, inhibiting the differentiation and activity of osteoclasts is important for maintaining bone mass. Several studies have revealed that the use of a low-frequency pulsed electromagnetic field (PEMF) is an effective method to treat osteoporosis. However, its exact mechanism remains to be fully clarified. Therefore, the present study was designed to examine the effects that PEMF exerts on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and intracellular reactive oxygen species (ROS) production in RAW264.7 cells. The viability of cells was determined using a Cell Counting Kit-8 assay, and gene and protein expression were investigated via reverse transcription-quantitative polymerase chain reaction and western blot analyses. Furthermore, microscopy was performed to detect the levels of intracellular ROS and tartrate-resistant acid phosphatase (TRAP). Following the culture of RAW264.7 cells with RANKL (50 ng/ml) for 4 days (3 h/day) under PEMF (75 Hz, 1 mt) exposure, it was observed that PEMF had an inhibitory effect on RANKL-induced osteoclastic differentiation. Multinucleated osteoclast formation, the activity of TRAP and the expression of osteoclastogenesis-associated genes, including cathepsin K, nuclear factor of activated T cells cytoplasmic 1 and TRAP, were significantly reduced by PEMF. Furthermore, PEMF effectively decreased the generation of intracellular ROS during osteoclastic differentiation. In addition, the results demonstrated that ROS are the key factor in osteoclast differentiation and formation. Reducing intracellular ROS with diphenylene-iodonium chloride significantly inhibited RANKL-induced osteoclast differentiation. Taken together, the results of the present study demonstrated that PEMF may inhibit RANKL-induced osteoclastogenesis by scavenging intracellular ROS. These results may provide the groundwork for future PEMF clinical applications in osteoclast-associated bone disease.