Abstract
Pulsed electromagnetic fields (PEMFs) have been considered a potential treatment modality for fracture healing, however, the mechanism of their action remains unclear. Mammalian target of rapamycin (mTOR) signaling may affect osteoblast proliferation and differentiation. This study aimed to assess the osteogenic differentiation of mesenchymal stem cells (MSCs) under PEMF stimulation and the potential involvement of mTOR signaling pathway in this process. PEMFs were generated by a novel miniaturized electromagnetic device. Potential changes in the expression of mTOR pathway components, including receptors, ligands and nuclear target genes, and their correlation with osteogenic markers and transcription factors were analyzed. Involvement of the mTOR pathway in osteogenesis was also studied in the presence of proinflammatory mediators. PEMF exposure increased cell proliferation and adhesion and the osteogenic commitment of MSCs even in inflammatory conditions. Osteogenic-related genes were over-expressed following PEMF treatment. Our results confirm that PEMFs contribute to activation of the mTOR pathway via upregulation of the proteins AKT, MAPP kinase, and RRAGA, suggesting that activation of the mTOR pathway is required for PEMF-stimulated osteogenic differentiation. Our findings provide insights into how PEMFs influence osteogenic differentiation in normal and inflammatory environments.
Highlights
Pulsed electromagnetic fields (PEMFs) have long been known to accelerate fracture repair[1]
The principal results of the present study revealed several novel findings regarding the events involved in the stimulation of the osteogenic differentiation of mesenchymal stem cells (MSCs) induced by PEMFs
They identified a significant role of mammalian target of rapamycin (mTOR) signaling during the differentiation driven by PEMF stimulation in an osteogenic microenvironment
Summary
Pulsed electromagnetic fields (PEMFs) have long been known to accelerate fracture repair[1]. That reaction involves a sequence of events, including protein adsorption on the surface of the implant, activation of complement and the coagulation system, recruitment of monocyte/macrophages and MSCs, activation and differentiation of these cells into functional macrophages, osteoclasts, and osteoblasts, respectively, and the formation of biological attachments between implant and new bone[11]. Serine/threonine kinase mammalian target of rapamycin (mTOR) has been shown to play an important role in osteoclast differentiation. It is activated by macrophage colony-stimulating factor, and its inhibition leads to decreased osteoclastogenesis[13,14]. It has been confirmed that the mTOR signaling pathway was involved in the regulation of apoptosis and autophagy in MSCs, and that its inhibition is able to attenuate age-related changes in MSCs18
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