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Review
. 2021 Jan 15;22(2):809.
doi: 10.3390/ijms22020809.

Pulsed Electromagnetic Field Stimulation in Osteogenesis and Chondrogenesis: Signaling Pathways and Therapeutic Implications

Katia Varani  1 , Fabrizio Vincenzi  1 , Silvia Pasquini  1 , Irene Blo  2 , Simona Salati  3 , Matteo Cadossi  3 , Monica De Mattei  2
Affiliations
Review

Pulsed Electromagnetic Field Stimulation in Osteogenesis and Chondrogenesis: Signaling Pathways and Therapeutic Implications

Katia Varani et al. Int J Mol Sci. .

Abstract

Mesenchymal stem cells (MSCs) are the main cell players in tissue repair and thanks to their self-renewal and multi-lineage differentiation capabilities, they gained significant attention as cell source for tissue engineering (TE) approaches aimed at restoring bone and cartilage defects. Despite significant progress, their therapeutic application remains debated: the TE construct often fails to completely restore the biomechanical properties of the native tissue, leading to poor clinical outcomes in the long term. Pulsed electromagnetic fields (PEMFs) are currently used as a safe and non-invasive treatment to enhance bone healing and to provide joint protection. PEMFs enhance both osteogenic and chondrogenic differentiation of MSCs. Here, we provide extensive review of the signaling pathways modulated by PEMFs during MSCs osteogenic and chondrogenic differentiation. Particular attention has been given to the PEMF-mediated activation of the adenosine signaling and their regulation of the inflammatory response as key player in TE approaches. Overall, the application of PEMFs in tissue repair is foreseen: (1) in vitro: to improve the functional and mechanical properties of the engineered construct; (2) in vivo: (i) to favor graft integration, (ii) to control the local inflammatory response, and (iii) to foster tissue repair from both implanted and resident MSCs cells.

Keywords: adenosine receptors; chondrogenic differentiation; mesenchymal stem cells; osteogenic differentiation; pulsed electromagnetic fields; tissue engineering.

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Conflict of interest statement

K.V., F.V., S.P., I.B., and M.D.M. declare no conflict of interest. S.S. is employee of IGEA SpA. M.C. is Vice President at IGEA S.p.A.

Figures

Figure 1
Figure 1
Effect of PEMFs on human osteoblasts and chondrocytes (no PEMFs: left panel, PEMFs exposure: right panel). PEMF stimulation induces an increase of A2A and A3ARs expression. The PEMF-induced upregulation enhances the anti-inflammatory downstream receptors signaling by decreasing NF-κB activation and the release of inflammatory mediators, such as IL-6, IL-8, and PGE2. Besides, PEMF-induced modulation of A2A and A3ARs results in a reduced VEGF release and increased cell proliferation and OPG production.
Figure 2
Figure 2
Effects of PEMFs stimulation on MSCs in view of cartilage (left panel) and bone (right panel) repair.
See this image and copyright information in PMC

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