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

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Abstract

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.

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All data generated or analyzed during this study are included in this published article.

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Acknowledgements

We thank Dr. Mattia Ferrarese, Department of Life Sciences and Biotechnology, University of Ferrara, for providing primers for VWF analysis.

Funding

This study was funded by grants from by IGEA S.p.A (Carpi, Italy) to MDM and from University of Ferrara to MDM and VB.

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Authors and Affiliations

  1. Department of Medical Sciences, University of Ferrara, Ferrara, Italy

    Monica De Mattei, Elena De Marchi & Deyanira Contartese

  2. Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy

    Silvia Grassilli, Agnese Pellati, Federica Brugnoli & Valeria Bertagnolo

  3. LTTA Centre, University of Ferrara, Ferrara, Italy

    Silvia Grassilli

  4. Laboratory Preclinical and Surgical Studies, IRCCS-Istituto Ortopedico Rizzoli, Bologna, Italy

    Deyanira Contartese

Authors
  1. Monica De Mattei
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  2. Silvia Grassilli
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  4. Federica Brugnoli
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  5. Elena De Marchi
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Contributions

MDM and VB was responsible for the study concept, supervised all the experiments and integrated the results; SG, AP, FB, EDM and DC performed experiments and prepared figures; VB and MDM drafted the manuscript with input and approval from all authors.

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Correspondence to Monica De Mattei or Valeria Bertagnolo.

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De Mattei, M., Grassilli, S., Pellati, A. et al. Pulsed Electromagnetic Fields Modulate miRNAs During Osteogenic Differentiation of Bone Mesenchymal Stem Cells: a Possible Role in the Osteogenic-angiogenic Coupling. Stem Cell Rev and Rep 16, 1005–1012 (2020). https://doi.org/10.1007/s12015-020-10009-6

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