Transcriptomic profiling of human mesenchymal stem cells using a pulsed electromagnetic-wave motion bioreactor system for enhanced osteogenic commitment and therapeutic potentials.

Traditional bioreactor systems involve the use of three-dimensional (3D) scaffolds or stem cell aggregates, limiting the accessibility to the production of cell-secreted biomolecules. Herein, we present the use a pulse electromagnetic fields (pEMFs)-assisted wave-motion bioreactor system for the dynamic and scalable culture of human bone marrow-derived mesenchymal stem cells (hBMSCs) with enhanced the secretion of various soluble factors with massive therapeutic potential. The present study investigated the influence of dynamic pEMF (D-pEMF) on the kinetic of hBMSCs. A 30-min exposure of pEMF (10V-1Hz, 5.82 G) with 35 oscillations per minute (OPM) rocking speed can induce the proliferation (1 × 105 â†’ 4.5 × 105) of hBMSCs than static culture. Furthermore, the culture of hBMSCs in osteo-induction media revealed a greater enhancement of osteogenic transcription factors under the D-pEMF condition, suggesting that D-pEMF addition significantly boosted hBMSCs osteogenesis. Additionally, the RNA sequencing data revealed a significant shift in various osteogenic and signaling genes in the D-pEMF group, further suggesting their osteogenic capabilities. In this research, we demonstrated that the combined effect of wave and pEMF stimulation on hBMSCs allows rapid proliferation and induces osteogenic properties in the cells. Moreover, our study revealed that D-pEMF stimuli also induce ROS-scavenging properties in the cultured cells. This study also revealed a bioactive and cost-effective approach that enables the use of cells without using any expensive materials and avoids the possible risks associated with them post-implantation.

Pulsed electromagnetic fields potentiate bone marrow mesenchymal stem cell chondrogenesis by regulating the Wnt/ß-catenin signaling pathway.

BACKGROUND: Pulsed electromagnetic fields (PEMFs) show promise as a treatment for knee osteoarthritis (KOA) by reducing inflammation and promoting chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). PURPOSE: To identify the efficacy window of PEMFs to induce BMSCs chondrogenic differentiation and explore the cellular mechanism under chondrogenesis of BMSCs in regular and inflammatory microenvironments. METHODS: BMSCs were exposed to PEMFs (75 Hz, 1.6/2/3/3.8 mT) for 7 and 14 days. The histology, proliferation, migration and chondrogenesis of BMSCs were assessed to identify the optimal parameters. Using these optimal parameters, transcriptome analysis was performed to identify target genes and signaling pathways, validated through immunohistochemical assays, western blotting, and qRT-PCR, with or without the presence of IL-1ß. The therapeutic effects of PEMFs and the effective cellular signaling pathways were evaluated in vivo. RESULTS: BMSCs treated with 3 mT PEMFs showed the optimal chondrogenesis on day 7, indicated by increased expression of ACAN, COL2A, and SOX9, and decreased levels of MMP3 and MMP13 at both transcriptional and protein levels. The advantages of 3 mT PEMFs diminished in the 14-day culture groups. Transcriptome analysis identified sFRP3 as a key molecule targeted by PEMF treatment, which competitively inhibited Wnt/ß-catenin signaling, regardless of IL-1ß presence or duration of exposure. This inhibition of the Wnt/ß-catenin pathway was also confirmed in a KOA mouse model following PEMF exposure. CONCLUSIONS: PEMFs at 75 Hz and 3 mT are optimal in inducing early-stage chondrogenic differentiation of BMSCs. The induction and chondroprotective effects of PEMFs are mediated by sFRP3 and Wnt/ß-catenin signaling, irrespective of inflammatory conditions.

Comparing the Effect of Bone-loading Exercises and Pulsed Electromagnetic Fields on Bone Turnover Markers in Women with Osteoporosis: A Randomized Clinical Trial Study Protocol.

Objective: Given the bone sensitivity to mechanical stimulus, bone-loading exercises and applying the Pulsed Electromagnetic Fields (PEMF(s)) are recommended for promoting bone strength. In this context, these two interventions 's effect on bone turnover markers (BTMs) in osteoporosis patients is yet to be clarified; consequently, an attempt is made in this study to compare the effect of these two interventions on bone turnover markers in women with Postmenopausal Osteoporosis (PMOP). Methods: This study is design as a randomized, single-center, three-arms, controlled trial. A total of 51 women with PMOP will be randomly assigned to three groups of 17, using opaque, sealed envelopes containing labels for A, B, and C groups. Group A) will receive bone-loading exercises, B) will follow the PEMF(s) and C) will be exposed to the combination of A and B. These three groups will require intervention for 24 sessions (2 sessions/week) next to their routine medical treatment (Alendronate+ Calcium+ Vitamin D). The primary outcome of this study is the serum biomarker of bone formation (bone-specific alkaline phosphatase, BSALP) and resorption (N-terminal telopeptide, NTX). The secondary outcomes consist of thoracic kyphosis angle, fear of falling, and quality of life. The outcomes are measured three times: at baseline, after 24 sessions of intervention, and at 12 weeks follow-up. A primary outcome will be measured and reported by a laboratory expert who is blinded to the participant grouping. Result: The trial has the code of ethics for research (IR.TUMS.FNM.REC.1401.126) and the code of Iranian Registry of Clinical Trials (IRCT) (IRCT20221202056687N1). Study results are expected to be available by mid-2024. Conclusion: This trial will provide new practical knowledge on the bone-loading exercises and PEMFS(s)'s effect on PMOP women. This knowledge is of the essence for physiotherapists, clinicians, other healthcare professionals, and policymakers in the healthcare system.

Exploring Mitochondrial Interactions with Pulsed Electromagnetic Fields: An Insightful Inquiry into Strategies for Addressing Neuroinflammation and Oxidative Stress in Diabetic Neuropathy.

Pulsed electromagnetic fields (PEMFs) are recognized for their potential in regenerative medicine, offering a non-invasive avenue for tissue rejuvenation. While prior research has mainly focused on their effects on bone and dermo-epidermal tissues, the impact of PEMFs on nervous tissue, particularly in the context of neuropathy associated with the diabetic foot, remains relatively unexplored. Addressing this gap, our preliminary in vitro study investigates the effects of complex magnetic fields (CMFs) on glial-like cells derived from mesenchymal cell differentiation, serving as a model for neuropathy of the diabetic foot. Through assessments of cellular proliferation, hemocompatibility, mutagenicity, and mitochondrial membrane potential, we have established the safety profile of the system. Furthermore, the analysis of microRNAs (miRNAs) suggests that CMFs may exert beneficial effects on cell cycle regulation, as evidenced by the upregulation of the miRNAs within the 121, 127, and 142 families, which are known to be associated with mitochondrial function and cell cycle control. This exploration holds promise for potential applications in mitigating neuropathic complications in diabetic foot conditions.

Pulsed electromagnetic fields used in regenerative medicine: An in vitro study of the skin wound healing proliferative phase.

Numerous studies have demonstrated the efficacy of extremely low frequency-pulsed electromagnetic fields (ELF-PEMF) in accelerating the wound healing process in vitro and in vivo. Our study focuses specifically on ELF-PEMF applied with the Magnomega® device and aims to assess their effect during the main stages of the proliferative phase of dermal wound closure, in vitro. Thus, after the characterization of the EMFs delivered by the Magnomega® unit, primary culture of human dermal fibroblasts (HDFs) were exposed, or not for the control culture, to 10-12 and 100 Hz ELF-PEMF. These parameters are used in clinical practice by physiotherapists in order to enhance healing of dermal lesions in patients. HDFs proliferation was first assessed and revealed an increase in the expression of one of the two genetic markers of cell proliferation tested (PCNA and MKI67), after initial exposure of the cells to 10-12 Hz PEMF. Next, migration of HDFs was investigated by performing scratch assays on HDF layers. The observed wound closure kinetics corroborate the early organization of actin stress fibers that was revealed in the cytoplasm of HDFs exposed to 100 Hz ELF-PEMF. Also, maturation of HDFs into myofibroblasts was significantly increased in cells exposed to 10-12 or to 100 Hz PEMF. The present study is the first to demonstrate, in vitro, an early stimulation of HDFs, after their exposure to ELF-PEMF delivered by the Magnomega® device, which could contribute to an acceleration of the wound healing process.

Current Evidence Using Pulsed Electromagnetic Fields in Osteoarthritis: A Systematic Review.

(1) Background: Osteoarthritis (OA) significantly impacts patients' quality of life and negatively affects public healthcare costs. The aim of this systematic review is to identify the effectiveness of pulsed electromagnetic fields (PEMFs) in OA treatment across different anatomical districts, determining pain reduction and overall improvement in the patient's quality of life. (2) Methods: In this systematic review following PRISMA guidelines, PubMed and Google Scholar were searched for randomized controlled trials involving patients with osteoarthritis undergoing PEMF therapy. Seventeen studies (1197 patients) were included. (3) Results: PEMF therapy demonstrated positive outcomes across various anatomical districts, primarily in knee osteoarthritis. Pain reduction, assessed through VAS and WOMAC scores, showed significant improvement (60% decrease in VAS, 42% improvement in WOMAC). The treatment duration varied (15 to 90 days), with diverse PEMF devices used. Secondary outcomes included improvements in quality of life, reduced medication usage, and enhanced physical function. (4) Conclusions: Diverse PEMF applications revealed promising results, emphasizing pain reduction and improvement in the quality of life of patients. The variability in the treatment duration and device types calls for further investigation. This review informs future research directions and potential advancements in optimizing PEMF therapies for diverse osteoarthritic manifestations.

Positive and Negative Effects of Administering a Magnetic Field to Patients with Rheumatoid Arthritis (RA).

Background: Magnetotherapy applied to patients with rheumatoid arthritis (RA) produces anti-inflammatory, analgesic and antioedema effects. Observations suggest that the beneficial and adverse effects of magnetotherapy are related to the parameters of the magnetic field applied. This study aimed to assess the positive and negative effects of magnetotherapy, taking into account the type of the field. Methods: This study involved 39 patients with RA, who were randomly assigned to two groups: SMF-static magnetic field (n = 18) and PEMF-low-frequency pulsed electromagnetic field (n = 21). The examinations carried out before and after the therapy included a general assessment of the functional status, assessment of pain severity, measurement of the duration and severity of morning stiffness, computer-aided measurement of the range of motion of the hand joints and measurement of the hand volume using water displacement method. The patients received kinesiotherapy and magnetotherapy, as determined by the randomisation. Results: The findings show improved functional status by 0.26 points on average (p = 0.0166) measured with the Health Assessment Questionnaire (HAQ-20), reduced pain by 2.2 points on average (p = 0.0000) on the Visual Analogue Scale (VAS), decreased duration of morning stiffness by 23.2 min on average (p = 0.0010) and reduced severity of morning stiffness by 15.2 points on average (p = 0.0010). The assessment of the dominant hand showed improved range of motion by 1.9 mm on average (p = 0.0036) and reduced volume by 0.9 mm3 on average (p = 0.0230). A significantly reduced duration and severity of morning stiffness was observed in the SMF group. Statistically significant changes in the HAQ-20 scores, range of motion and the volume of the dominant hand were identified in the PEMF group. Conclusions: Magnetic fields improved the functional status and reduced pain, morning stiffness and swelling in the hand. A static magnetic field may be more effective in reducing morning stiffness, whereas a pulsed magnetic field may, to a greater extent, improve function and reduce swelling in the rheumatoid hand. The effects of magnetotherapy reported so far require further observation.

Pulsed Electromagnetic Fields (PEMFs) Trigger Cell Death and Senescence in Cancer Cells.

The currently available anti-cancer therapies, such as gamma-radiation and chemotherapeutic agents, induce cell death and cellular senescence not only in cancer cells but also in the adjacent normal tissue. New anti-tumor approaches focus on limiting the side effects on normal cells. In this frame, the potential anti-tumor properties of Pulsed Electromagnetic Fields (PEMFs) through the irradiation of breast cancer epithelial cells (MCF-7 and MDA-MB-231) and normal fibroblasts (FF95) were investigated. PEMFs had a frequency of 8 Hz, full-square wave type and magnetic flux density of 0.011 T and were applied twice daily for 5 days. The data collected showcase that PEMF application decreases the proliferation rate and viability of breast cancer cells while having the opposite effect on normal fibroblasts. Moreover, PEMF irradiation induces cell death and cellular senescence only in breast cancer cells without any effect in the non-cancerous cells. These findings suggest PEMF irradiation as a novel, non-invasive anti-cancer strategy that, when combined with senolytic drugs, may eliminate both cancer and the remaining senescent cells, while simultaneously avoiding the side effects of the current treatments.

Observation of the Short-term Efficacy of Technetium-99 Conjugated with Methylene Diphosphonate Combined Therapy in the Treatment of Postmenopausal Osteoporosis.

OBJECTIVE: To investigate the short-term efficacy and safety of Yunke (technetium-99 conjugated methylene diphosphonate) combined with pulsed electromagnetic field (PEMF) and Gukang capsule in the treatment of postmenopausal osteoporosis (PMOP). METHODS: A total of 112 patients with PMOP who received treatment in the Department of Nuclear Medicine of the hospital from January 2019 to June 2020 were selected and randomly divided into 4 groups of 28 patients each. Group A received Yunke and PEMFs, group B received Gukang capsules and PEMFs, group C received Yunke and Gukang capsules and PEMFs, and group D received PEMFs. All groups were given adequate amounts of calcium and active vitamin D. Intervention 2 sessions of 3 months each. Outcome measures were bone mineral density (BMD) and pain improvement. RESULTS: Compared with 1 course of treatment, the symptoms of bone pain were relieved more significantly after 2 courses of treatment in group A (50.0% vs. 64.3%), group B (46.4% vs. 64.3%), group C (78.6% vs. 92.9%) and group D (21.4% vs. 28.6%) (P < 0.05). After 2 courses of treatment, bone pain symptoms were less relieved in group A (96.4% vs. 64.3%), group B (96.4% vs. 64.3%), and group D (96.4% vs. 28.6%) compared with group C (P < 0.05). Compared with group C, BMD values of L4 vertebrae and femoral neck were significantly decreased in groups A, B, and D (P < 0.05). Compared with those before treatment, BMD of L4 vertebrae and femoral neck increased significantly in groups A, B, C, and D after 2 courses of treatment (P < 0.05). CONCLUSION: Yunke combined therapy can effectively relieve the pain symptoms, increase BMD, and reduce the risk of fracture in patients with PMOP in a short period, which is an effective method for the treatment of PMOP.

Signalling pathways underlying pulsed electromagnetic fields in bone repair.

Pulsed electromagnetic field (PEMF) stimulation is a prospective non-invasive and safe physical therapy strategy for accelerating bone repair. PEMFs can activate signalling pathways, modulate ion channels, and regulate the expression of bone-related genes to enhance osteoblast activity and promote the regeneration of neural and vascular tissues, thereby accelerating bone formation during bone repair. Although their mechanisms of action remain unclear, recent studies provide ample evidence of the effects of PEMF on bone repair. In this review, we present the progress of research exploring the effects of PEMF on bone repair and systematically elucidate the mechanisms involved in PEMF-induced bone repair. Additionally, the potential clinical significance of PEMF therapy in fracture healing is underscored. Thus, this review seeks to provide a sufficient theoretical basis for the application of PEMFs in bone repair.

The prevention effect of pulsed electromagnetic fields treatment on senile osteoporosis in vivo via improving the inflammatory bone microenvironment.

This study aimed to assess PEMF in a rat model of senile osteoporosis and its relationship with NLRP3-mediated low-grade inflammation in the bone marrow microenvironment. A total of 24 Sprague Dawley (SD) rats were included in this study. Sixteen of them were 24-month natural-aged male SD rats, which were randomly distributed into the Aged group and the PEMF group (n = 8 per group). The remaining 8 3-month -old rats were used as the Young positive control group (n = 8). Rats in the PEMF group received 12 weeks of PEMF with 40 min/day, five days per week, while the other rats received placebo PEMF intervention. Bone mineral density/microarchitecture, serum levels of CTX-1 and P1CP, and NLRP3-related signaling genes and proteins in rat bone marrow were then analyzed. The 12-week of PEMF showed significant mitigation of aging-induced bone loss and bone microarchitecture deterioration, i.e. PEMF increased the bone mineral density of the proximal femur and L5 vertebral body and improved parameters of the proximal tibia and L4 vertebral body. Further analysis showed that PEMF reversed aging-induced bone turnover, specifically, decreased serum CTX-1 and elevated serum P1CP. Furthermore, PEMF also dramatically inhibited NLRP3-mediated low-grade inflammation in the bone marrow, i.e. PEMF inhibited the levels of NLRP3, proCaspase1, cleaved Caspase1, IL-1ß, and GSDMD-N. The study demonstrated that PEMF could mitigate the aging-induced bone loss and reverses the deterioration of bone microarchitecture probably through inhibiting NLRP3-mediated low-grade chronic inflammation to improve the inflammatory bone microenvironment in aged rats.

Peripheral magnetic stimulation for chronic peripheral neuropathic pain: A systematic review and meta-analysis.

OBJECTIVES: To provide a systematic review of the literature on the effects of peripheral magnetic stimulation (PMS) in the treatment of chronic peripheral neuropathic pain. METHODS: A systematic search of MEDLINE, EMBASE, CENTRAL, CINHAL, Web of Science, and ProQuest was conducted from inception to July 2023 to identify studies of any design published in English language that enrolled adult patients (≥18 years) that received PMS for treatment of a chronic peripheral neuropathic pain disorder (pain > 3 months). RESULTS: Twenty-three studies were identified which included 15 randomized controlled trials (RCTs), five case series, two case reports, and one non-randomized trial. PMS regimens varied across studies and ranged from 5 to 240 min per session over 1 day to 1 year of treatment. Results across included studies were mixed, with some studies suggesting benefits while others showing no significant differences. Of nine placebo-controlled RCTs, four reported statistically significant findings in favor of PMS use. In the meta-analysis, PMS significantly reduced pain scores compared to control within 0-1 month of use (mean difference -1.64 on a 0-10 numeric rating scale, 95% confidence interval -2.73 to -0.56, p = 0.003, I2 = 94%, 7 studies [264 participants], very low quality of evidence), but not at the 1-3 months and >3 months of PMS use (very low and low quality of evidence, respectively). Minimal to no adverse effects were reported with PMS use. DISCUSSION: There is limited and low-quality evidence to make definitive recommendations on PMS usage, however, the available data is encouraging, especially for short-term applications of this novel modality. Large high-quality randomized controlled trials are required to establish definitive efficacy and safety effects of PMS.

Pulsed Electromagnetic Field Stimulation in Lumbar Spine Fusion for Patients With Risk Factors for Pseudarthrosis.

BACKGROUND: Lumbar spinal fusion surgeries are increasing steadily due to an aging and ever-growing population. Patients undergoing lumbar spinal fusion surgery may present with risk factors that contribute to complications, pseudarthrosis, prolonged pain, and reduced quality of life. Pulsed electromagnetic field (PEMF) stimulation represents an adjunct noninvasive treatment intervention that has been shown to improve successful fusion and patient outcomes following spinal surgery. METHODS: A prospective, multicenter study investigated PEMF as an adjunct therapy to lumbar spinal fusion procedures in patients at risk for pseudarthrosis. Patients with at least 1 of the following risk factors were enrolled: prior failed fusion, multilevel fusion, nicotine use, osteoporosis, or diabetes. Fusion status was determined by radiographic imaging, and patient-reported outcomes were also evaluated. RESULTS: A total of 142 patients were included in the analysis. Fusion status was assessed at 12 months follow-up where 88.0% (n = 125/142) of patients demonstrated successful fusion. Fusion success for patients with 1, 2+, or 3+ risk factors was 88.5%, 87.5%, and 82.3%, respectively. Significant improvements in patient-reported outcomes using the Short Form 36, EuroQol 5 Dimension (EQ-5D) survey, Oswestry Disability Index, and visual analog scale for back and leg pain were also observed compared with baseline scores (P < 0.001). A favorable safety profile was observed. PEMF treatment showed a positive benefit-risk profile throughout the 6-month required use period. CONCLUSIONS: The addition of PEMF as an adjunct treatment in patients undergoing lumbar spinal surgery provided a high rate of successful fusion with significant improvements in pain, function, and quality of life, despite having risk factors for pseudarthrosis. CLINICAL RELEVANCE: PEMF represents a useful tool for adjunct treatment in patients who have undergone lumbar spinal surgery. Treatment with PEMF may result in improved fusion and patient-reported outcomes, regardless of risk factors. TRIAL REGISTRATION: NCT03176303.

Targeting Adenosine Signalling in Knee Chondropathy: The Combined Action of Polydeoxyribonucleotide and Pulsed Electromagnetic Fields: A Current Concept Review.

Chondropathy of the knee is one of the most frequent degenerative cartilage pathologies with advancing age. Scientific research has, in recent years, advanced new therapies that target adenosine A2 receptors, which play a significant role in human health against many disease states by activating different protective effects against cell sufferance and damage. Among these, it has been observed that intra-articular injections of polydeoxyribonucleotides (PDRN) and Pulsed Electromagnetic Fields (PEMF) can stimulate the adenosine signal, with significant regenerative and healing effects. This review aims to depict the role and therapeutic modulation of A2A receptors in knee chondropathy. Sixty articles aimed at providing data for our study were included in this review. The present paper highlights how intra-articular injections of PDRN create beneficial effects by reducing pain and improving functional clinical scores, thanks to their anti-inflammatory action and the important healing and regenerating power of the stimulation of cell growth, production of collagen, and the extracellular matrix. PEMF therapy is a valid option in the conservative treatment of different articular pathologies, including early OA, patellofemoral pain syndrome, spontaneous osteonecrosis of the knee (SONK), and in athletes. PEMF could also be used as a supporting therapy after an arthroscopic knee procedure total knee arthroplasty to reduce the post-operative inflammatory state. The proposal of new therapeutic approaches capable of targeting the adenosine signal, such as the intra-articular injection of PDRN and the use of PEMF, has shown excellent beneficial results compared to conventional treatments. These are presented as an extra weapon in the fight against knee chondropathy.

Pulsed Electromagnetic Fields Improved Peripheral Nerve Regeneration After Delayed Repair of One Month.

The goal of this study was to determine if postoperative pulsed electromagnetic fields (PEMFs) could improve the neuromuscular rehabilitation after delayed repair of peripheral nerve injuries. Thirty-six Sprague-Dawley rats were randomly divided into sham group, control group, and PEMFs group. The sciatic nerves were transected except for the control group. One month later, the nerve ends of the former two groups were reconnected. PEMFs group of rats was subjected to PEMFs thereafter. Control group and sham group received no treatment. Four and 8 weeks later, morphological and functional changes were measured. Four and eight weeks postoperatively, compared to sham group, the sciatic functional indices (SFIs) of PEMFs group were higher. More axons regenerated distally in PEMFs group. The fiber diameters of PEMFs group were larger. However, the axon diameters and myelin thicknesses were not different between these two groups. The brain-derived neurotrophic factor and vascular endothelial growth factor expressions were higher in PEMFs group after 8 weeks. Semi-quantitative IOD analysis for the intensity of positive staining indicated that there were more BDNF, VEGF, and NF200 in PEMFs group. It's concluded that PEMFs have effect on the axonal regeneration after delayed nerve repair of one month. The upregulated expressions of BDNF and VEGF may play roles in this process. © 2023 Bioelectromagnetics Society.

First Metatarsal Bilateral Stress Fracture: A Case Report.

Introduction: Metatarsal stress fractures typically occur in the second and third metatarsus metaphysis, with only rare cases in the fourth and first. The main factors influencing its onset are repetitive stress from prolonged training, biomechanical factors and bone weakness. There is only a paucity of literature documenting first metatarsal stress fractures; the authors present a rare bilateral first metatarsal stress fracture. Case Report: A Caucasian 52-years-old amateur female runner with no other risk factors or medical condition was admitted in our institute with complaints of severe bilateral forefoot pain for 2 weeks arisen after a 20 km run of an amateur race. The patient presented bilateral hallux valgus (HVA) and advanced osteoarthritis of the first metatarsal-phalangeal joint, which is not usually considered a biomechanical risk factor for metatarsal stress fractures. Radiographs of both feet showed linear sclerosis, perpendicular to the diaphysis of the first metatarsal, approximatively in the half of the bone. Signs of osteoarthritis of the first metatarsal-phalangeal were also detected bilaterally.The patient was treated with rest, bilateral post-operative rocker sole shoes that she has worn for 6 weeks, cryotherapy, analgesics as needed and pulsed electromagnetic fields for 8 h per day for 40 days with a complete resolution of symptoms and the previous radiological findings. Conclusion: The authors believed that the bilateral HVA condition could be considered an indirect sign of overuse, and it may be investigated and eventually treated as a responsible for this pathologic condition.

[Effect of pulsed electromagnetic fields on mesenchymal stem cell-derived exosomes in inhibiting chondrocyte apoptosis].

The study aims to explore the effect of mesenchymal stem cells-derived exosomes (MSCs-Exo) on staurosporine (STS)-induced chondrocyte apoptosis before and after exposure to pulsed electromagnetic field (PEMF) at different frequencies. The AMSCs were extracted from the epididymal fat of healthy rats before and after exposure to the PEMF at 1 mT amplitude and a frequency of 15, 45, and 75 Hz, respectively, in an incubator. MSCs-Exo was extracted and identified. Exosomes were labeled with DiO fluorescent dye, and then co-cultured with STS-induced chondrocytes for 24 h. Cellular uptake of MSC-Exo, apoptosis, and the protein and mRNA expression of aggrecan, caspase-3 and collagenⅡA in chondrocytes were observed. The study demonstrated that the exposure of 75 Hz PEMF was superior to 15 and 45 Hz PEMF in enhancing the effect of exosomes in alleviating chondrocyte apoptosis and promoting cell matrix synthesis. This study lays a foundation for the regulatory mechanism of PEMF stimulation on MSCs-Exo in inhibiting chondrocyte apoptosis, and opens up a new direction for the prevention and treatment of osteoarthritis.

Bone Deterioration in Response to Chronic High-Altitude Hypoxia Is Attenuated by a Pulsed Electromagnetic Field Via the Primary Cilium/HIF-1α Axis.

Chronic high-altitude hypoxia induces irreversible abnormalities in various organisms. Emerging evidence indicates that hypobaric hypoxia markedly suppresses bone mass and bone strength. However, few effective means have been identified to prevent such bone deficits. Here, we assessed the potential of pulsed electromagnetic fields (PEMFs) to noninvasively resist bone deterioration induced by hypobaric hypoxia. We observed that exogenous PEMF treatment at 15 Hz and 20 Gauss (Gs) improved the cancellous and cortical bone mass, bone microstructure, and skeletal mechano-properties in rats subjected to chronic exposure of hypobaric hypoxia simulating an altitude of 4500 m for 6 weeks by primarily modulating osteoblasts and osteoblast-mediated bone-forming activity. Moreover, our results showed that whereas PEMF stimulated the functional activity of primary osteoblasts in hypoxic culture in vitro, it had negligible effects on osteoclasts and osteocytes exposed to hypoxia. Mechanistically, the primary cilium was found to function as the major electromagnetic sensor in osteoblasts exposed to hypoxia. The polycystins PC-1/PC-2 complex was identified as the primary calcium channel in the primary cilium of hypoxia-exposed osteoblastic cells responsible for the detection of external PEMF signals, and thereby translated these biophysical signals into intracellular biochemical events involving significant increase in the intracellular soluble adenylyl cyclase (sAC) expression and subsequent elevation of cyclic adenosine monophosphate (cAMP) concentration. The second messenger cAMP inhibited the transcription of oxygen homeostasis-related hypoxia-inducible factor 1-alpha (HIF-1α), and thus enhanced osteoblast differentiation and improved bone phenotype. Overall, the present study not only advances our understanding of bone physiology at high altitudes, but more importantly, proposes effective means to ameliorate high altitude-induced bone loss in a noninvasive and cost-effective manner. © 2023 American Society for Bone and Mineral Research (ASBMR).

Pulsed electromagnetic field attenuates bone fragility in estrogen-deficient osteoporosis in rats.

BACKGROUND: The pulsed electromagnetic fields (PEMFs) seem effective in increasing bone mineral density and promoting osteogenesis and bone healing. OBJECTIVE: To examine the effect of two different modalities of PEMFs therapy in comparison with the recommended pharmacological treatment on experimental osteoporosis in rats. METHODS: The experimental model of estrogen-deficient osteoporosis induced by ovariectomy was used in this study. The animals were exposed to PEMFs of various frequencies (40 Hz and 25 Hzk), intensities (10 mT and 36.4 µT), lengths of exposure, and the effects were compared with the standard treatment with pamidronate, vitamin D, and calcium supplementation. RESULTS: The application of PEMF40Hz, significantly reduced the osteoporotic bone loss in female rats that were confirmed with biochemical, biomechanical, and histological analyses. These effects were more pronounced than in osteoporotic animals treated with pamidronate, vitamin D, and calcium supplementation. On the contrary, the exposure to PEMF25Hz did not show restorative effects but led to further progression of osteoporosis. CONCLUSION: The exposure to PEMF40Hz, significantly restored osteoporosis and attenuated bone fragility in comparison to the rats exposed to PEMF25Hz or those treated with pamidronate, vitamin D, and calcium supplementation.

Effect of pulsed electromagnetic fields on mesenchymal stem cell-derived exosomes in inhibiting chondrocyte apoptosis / 生物医学工程学杂志

The study aims to explore the effect of mesenchymal stem cells-derived exosomes (MSCs-Exo) on staurosporine (STS)-induced chondrocyte apoptosis before and after exposure to pulsed electromagnetic field (PEMF) at different frequencies. The AMSCs were extracted from the epididymal fat of healthy rats before and after exposure to the PEMF at 1 mT amplitude and a frequency of 15, 45, and 75 Hz, respectively, in an incubator. MSCs-Exo was extracted and identified. Exosomes were labeled with DiO fluorescent dye, and then co-cultured with STS-induced chondrocytes for 24 h. Cellular uptake of MSC-Exo, apoptosis, and the protein and mRNA expression of aggrecan, caspase-3 and collagenⅡA in chondrocytes were observed. The study demonstrated that the exposure of 75 Hz PEMF was superior to 15 and 45 Hz PEMF in enhancing the effect of exosomes in alleviating chondrocyte apoptosis and promoting cell matrix synthesis. This study lays a foundation for the regulatory mechanism of PEMF stimulation on MSCs-Exo in inhibiting chondrocyte apoptosis, and opens up a new direction for the prevention and treatment of osteoarthritis.