Translational Medicine Department, University of Ferrara, Ferrara, 44121, Italy.
Institute of Polymers, Composites and Biomaterials - National Research Council (IPCB-CNR), Naples, 80125, Italy.
Int J Nanomedicine. 2024 Aug 24;19:8695-8707. doi: 10.2147/IJN.S470901. eCollection 2024.
In the process of bone regeneration, a prominent role is played by macrophages involved in both the initial inflammation and the regeneration/vascularization phases, due to their M2 anti-inflammatory phenotype. Together with osteoclasts, they participate in the degradation of the bone matrix if the inflammatory process does not end. In this complex scenario, recently, much attention has been paid to extracellular communication mediated by nanometer-sized vesicles, with high information content, called exosomes (EVs). Considering these considerations, the purpose of the present work is to demonstrate how the presence of a pulsed electromagnetic field (PEMF) can positively affect communication through EVs.
To this aim, macrophages and osteoclasts were treated in vitro with PEMF and analyzed through molecular biology analysis and by electron microscopy. Moreover, EVs produced by macrophages were characterized and used to verify their activity onto osteoclasts.
The results confirmed that PEMF not only reduces the inflammatory activity of macrophages and the degradative activity of osteoclasts but that the EVS produced by macrophages, obtained from PEMF treatment, positively affect osteoclasts by reducing their activity.
The co-treatment of PEMF with M2 macrophage-derived EVs (M2-EVs) decreased osteoclastogenesis to a greater degree than separate treatments.
在骨再生过程中,巨噬细胞发挥着重要作用,它们参与初始炎症和再生/血管生成阶段,因其 M2 抗炎表型。如果炎症过程不结束,它们与破骨细胞一起参与骨基质的降解。在这种复杂的情况下,最近,人们越来越关注由纳米大小的囊泡介导的具有高信息含量的细胞外通讯,称为外泌体 (EVs)。基于这些考虑,本研究的目的是证明脉冲电磁场 (PEMF) 的存在如何通过 EVs 积极影响通讯。
为此,用 PEMF 体外处理巨噬细胞和破骨细胞,并通过分子生物学分析和电子显微镜进行分析。此外,还对巨噬细胞产生的 EVs 进行了表征,并用于验证其对破骨细胞的活性。
结果证实,PEMF 不仅降低了巨噬细胞的炎症活性和破骨细胞的降解活性,而且巨噬细胞产生的 EVs(来自 PEMF 处理)通过降低其活性对破骨细胞产生积极影响。
与单独治疗相比,PEMF 与 M2 巨噬细胞衍生的 EVs (M2-EVs) 的共同治疗使破骨细胞生成减少的程度更大。