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Int J Mol Sci. 2020 Mar 19;21(6). pii: E2104. doi: 10.3390/ijms21062104.

Bone Morphogenetic Protein-2 Signaling in the Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells Induced by Pulsed Electromagnetic Fields.

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Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy.
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy.
IGEA Clinical Biophysics, Carpi, 41012 Modena, Italy.
Department of Biomedical and Specialty Surgical Sciences, Azienda Ospedaliero-Universitaria di Ferrara-Arcispedale Sant'Anna, University of Ferrara, 44124 Ferrara, Italy.
Laboratory Preclinical and Surgical Studies, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.


Pulsed electromagnetic fields (PEMFs) are clinically used with beneficial effects in the treatment of bone fracture healing. This is due to PEMF ability to favor the osteogenic differentiation of mesenchymal stem cells (MSCs). Previous studies suggest that PEMFs enhance the osteogenic activity of bone morphogenetic protein-2 (BMP2) which is used in various therapeutic interventions. This study investigated the molecular events associated to the synergistic activity of PEMFs and BMP2 on osteogenic differentiation. To this aim, human MSCs (hMSCs) were exposed to PEMFs (75 Hz, 1.5 mT) in combination with BMP2, upon detection of the minimal dose able to induce differentiation. Changes in the expression of BMP signaling pathway genes including receptors and ligands, as well as in the phosphorylation of BMP downstream signaling proteins, such as SMAD1/5/8 and MAPK, were analyzed. Results showed the synergistic activity of PEMFs and BMP2 on osteogenic differentiation transcription factors and markers. The PEMF effects were associated to the increase in BMP2, BMP6, and BMP type I receptor gene expression, as well as SMAD1/5/8 and p38 MAPK activation. These results increase knowledge concerning the molecular events involved in PEMF stimulation showing that PEMFs favor hMSCs osteogenic differentiation by the modulation of BMP signaling components.


BMP; mesenchymal stem cells; osteogenic differentiation; pulsed electromagnetic fields

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