EMF-induced mesenchymal stem cell migration is mediated by SOCE-dependent calcium influx and modulated by ROCK signaling.

PAPER pubmed Journal of bioenergetics and biomembranes 2026 In vitro study Effect: benefit Evidence: Moderate

Read original paper → DOI: 10.1007/s10863-026-10085-2 PMID: 41670876 Evidence Lab

Abstract

Abstract Electromagnetic field (EMF) exposure promotes mesenchymal stem cell (MSCs) migration, a critical process in regenerative medicine. While calcium (Ca²⁺) signaling is implicated, the primary Ca²⁺ entry pathway and its downstream mechanisms remain elusive. This study investigates the hypothesis that store-operated calcium entry (SOCE) serves as a major Ca²⁺ influx mechanism and modulates the ROCK pathway to drive EMF-induced MSCs migration. Rat bone marrow-derived MSCs were exposed to a 50 Hz, 5 mT sinusoidal EMF. Cell migration was assessed via Transwell assays. Intracellular Ca²⁺ and SOCE activity were measured using Fluo-4 AM. Transcriptomic profiling was performed by RNA sequencing. Cytoskeletal reorganization (F-actin, acetylated α-tubulin) and protein expression (Orai1, ROCK1/2) were analyzed by immunofluorescence and western blotting, using pharmacological inhibitors (BTP2 for SOCE, Y-27632 for ROCK) and calcium chelators to dissect the pathway. EMF exposure significantly enhanced MSCs migration and activated calcium signaling pathways. This pro-migratory effect was strictly dependent on extracellular Ca²⁺ influx and was abolished by SOCE inhibition with BTP2. EMF upregulated the SOCE channel Orai1 and enhanced SOCE activity. Crucially, EMF suppressed ROCK1/2 expression under normal conditions, but this suppression was not reversed under SOCE inhibition or in low-calcium medium and EMF exposure increased ROCK1/2 expression in Ca²⁺-free medium (with 2 mM EGTA). SOCE inhibition also attenuated EMF-induced cytoskeletal reorganization, including perinuclear accumulation of acetylated α-tubulin and F-actin polymerization. Our findings establish SOCE-mediated Ca²⁺ influx as the critical driver of EMF-promoted MSCs migration. This process involves the upregulation of Orai1 and elicits a biphasic, context-dependent modulation of the ROCK pathway. The pro-migratory phenotype requires the synergy of SOCE-dependent Ca²⁺ influx and ROCK downregulation, leading to coordinated cytoskeletal remodeling. This study redefines the mechanistic understanding of EMF bioeffects, highlighting SOCE as a key regulator that integrates calcium signaling with cytoskeletal dynamics to control cell migration.

AI evidence extraction

At a glance

Study type

In vitro study

Effect direction

benefit

Population

rat bone marrow-derived mesenchymal stem cells

Sample size

—

Exposure

ELF · 0.05 MHz

Evidence strength

Moderate

Confidence: 70% · Peer-reviewed: yes

Main findings

Exposure to a 50 Hz, 5 mT sinusoidal EMF significantly enhanced migration of rat mesenchymal stem cells via SOCE-dependent calcium influx. EMF upregulated the SOCE channel Orai1 and modulated ROCK1/2 expression in a calcium-dependent manner. Inhibition of SOCE abolished the pro-migratory effect and attenuated cytoskeletal reorganization, indicating SOCE-mediated calcium influx is critical for EMF-induced MSC migration involving ROCK pathway modulation.

Outcomes measured

mesenchymal stem cell migration
intracellular calcium signaling
SOCE activity
ROCK1/2 protein expression
cytoskeletal reorganization

Limitations

Study conducted in vitro using rat cells, limiting direct extrapolation to humans or in vivo conditions
Specific exposure duration and SAR values not reported
Mechanistic focus limits assessment of broader biological effects

View raw extracted JSON

{
    "study_type": "in_vitro",
    "exposure": {
        "band": "ELF",
        "source": null,
        "frequency_mhz": 0.05000000000000000277555756156289135105907917022705078125,
        "sar_wkg": null,
        "duration": null
    },
    "population": "rat bone marrow-derived mesenchymal stem cells",
    "sample_size": null,
    "outcomes": [
        "mesenchymal stem cell migration",
        "intracellular calcium signaling",
        "SOCE activity",
        "ROCK1/2 protein expression",
        "cytoskeletal reorganization"
    ],
    "main_findings": "Exposure to a 50 Hz, 5 mT sinusoidal EMF significantly enhanced migration of rat mesenchymal stem cells via SOCE-dependent calcium influx. EMF upregulated the SOCE channel Orai1 and modulated ROCK1/2 expression in a calcium-dependent manner. Inhibition of SOCE abolished the pro-migratory effect and attenuated cytoskeletal reorganization, indicating SOCE-mediated calcium influx is critical for EMF-induced MSC migration involving ROCK pathway modulation.",
    "effect_direction": "benefit",
    "limitations": [
        "Study conducted in vitro using rat cells, limiting direct extrapolation to humans or in vivo conditions",
        "Specific exposure duration and SAR values not reported",
        "Mechanistic focus limits assessment of broader biological effects"
    ],
    "evidence_strength": "moderate",
    "confidence": 0.6999999999999999555910790149937383830547332763671875,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "electromagnetic field",
        "mesenchymal stem cells",
        "calcium signaling",
        "store-operated calcium entry",
        "SOCE",
        "ROCK pathway",
        "cell migration",
        "cytoskeletal remodeling"
    ],
    "suggested_hubs": []
}

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AI-extracted fields are generated from the abstract/metadata and may be incomplete or incorrect. This content is for informational purposes only and is not medical advice.

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