Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy.
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy.
Int J Mol Sci. 2020 Mar 19;21(6):2104. doi: 10.3390/ijms21062104.
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.
脉冲电磁场（PEMFs）在治疗骨折愈合方面具有临床应用价值，能促进间充质干细胞（MSCs）的成骨分化。先前的研究表明，PEMFs 能增强骨形成蛋白 2（BMP2）的成骨活性，BMP2 被广泛应用于各种治疗干预中。本研究旨在探讨 PEMFs 和 BMP2 协同促进成骨分化相关的分子事件。为此，我们将人 MSCs（hMSCs）暴露于 PEMFs（75 Hz，1.5 mT）中，同时加入 BMP2，检测能够诱导分化的最小剂量。分析 BMP 信号通路基因（包括受体和配体）的表达变化，以及 BMP 下游信号蛋白（如 SMAD1/5/8 和 MAPK）的磷酸化。结果表明，PEMFs 和 BMP2 协同促进成骨分化转录因子和标志物的表达。PEMF 的作用与 BMP2、BMP6 和 BMP 型 I 受体基因表达的增加以及 SMAD1/5/8 和 p38 MAPK 的激活有关。这些结果增加了我们对 PEMF 刺激涉及的分子事件的了解，表明 PEMFs 通过调节 BMP 信号成分促进 hMSCs 的成骨分化。
