Modulation of Macrophage Activity by Pulsed Electromagnetic Fields in the Context of Fracture Healing

Abstract

Delayed fracture healing and fracture non-unions impose an enormous burden on individuals and society. Successful healing requires tight communication between immune cells and bone cells. Macrophages can be found in all healing phases. Due to their high plasticity and long life span, they represent good target cells for modulation. In the past, extremely low frequency pulsed electromagnet fields (ELF-PEMFs) have been shown to exert cell-specific effects depending on the field conditions. Thus, the aim was to identify the specific ELF-PEMFs able to modulate macrophage activity to indirectly promote mesenchymal stem/stromal cell (SCP-1 cells) function. After a blinded screening of 22 different ELF-PEMF, two fields (termed A and B) were further characterized as they diversely affected macrophage function. These two fields have similar fundamental frequencies (51.8 Hz and 52.3 Hz) but are emitted in different groups of pulses or rather send–pause intervals. Macrophages exposed to field A showed a pro-inflammatory function, represented by increased levels of phospho-Stat1 and CD86, the accumulation of ROS, and increased secretion of pro-inflammatory cytokines. In contrast, macrophages exposed to field B showed anti-inflammatory and pro-healing functions, represented by increased levels of Arginase I, increased secretion of anti-inflammatory cytokines, and growth factors are known to induce healing processes. The conditioned medium from macrophages exposed to both ELF-PEMFs favored the migration of SCP-1 cells, but the effect was stronger for field B. Furthermore, the conditioned medium from macrophages exposed to field B, but not to field A, stimulated the expression of extracellular matrix genes in SCP-1 cells, i.e., COL1A1, FN1, and BGN. In summary, our data show that specific ELF-PEMFs may affect immune cell function. Thus, knowing the specific ELF-PEMFs conditions and the underlying mechanisms bears great potential as an adjuvant treatment to modulate immune responses during pathologies, e.g., fracture healing.

Maqui Berry and Ginseng Extracts Reduce Cigarette Smoke-Induced Cell Injury in a 3D Bone Co-Culture Model

“…The electrophoresis was carried out at 90 V for 60 min to separate the PCR products. Finally, the intensity of the bands was quantitatively analyzed by ImageJ (NIH, Bethesda, MD, USA) [ 47 ].…”

“…The protein concentrations were determined with the micro-Lowry method [ 15 ]. As previously described [ 47 ], 25 μg of total protein was separated by 12% acrylamide gels (100 V, 180 min) and then transferred onto a nitrocellulose blotting membrane (100 mA, 180 min). Ponceaus staining was used to visually ensure adequate protein transfer.…”

A Novel Method to Achieve Precision and Reproducibility in Exposure Parameters for Low-Frequency Pulsed Magnetic Fields in Human Cell Cultures

“…As a further verification of the ability of our system to provide biologically relevant and well-controlled exposures to cell cultures, we tested two additional short-pulsed signals E and F (CIT#81 and CIT#96), which were featured in studies of [ 54 , 56 ]. With Signal E ( Figure 5 E, CIT#81), we showed that a signal with in the -range ( s) is also able to significantly decrease the inflammatory response in HEK-Blue™ hTLR4 cells by roughly .…”

“…For Figure 2 C,D, the duty cycle has been adjusted so that equals that of signal B and A, respectively, see Table 2 . In addition, we used two PEMF signals with a proprietary, monopolar, triangular shape and a short pulse length s (so-called CIT-pulse [ 21 , 56 ]).…”

The Role of SOCS2 Cytokine Signaling Suppressor in the Regulation of ProInflammatory Activity of Whole Blood Cells after Lower Respiratory Tract Infection

“…В этих условиях показана возможность супрессора цитокиновой сигнализации SOCS2 модулировать активность JAK/STAT-сигнального пути и ядерного фактора транскрипции NF-κB, регулируя тем самым провоспалительную реактивность ИКК и их чувствительность к цитокинам. При этом противовоспалительное действие SOCS2, очевидно определяющееся его влиянием на уровень отдельных компонентов ядерного фактора транскрипции NF-κB, сочетается с иммунорегулирующим влиянием, выражающимся в изменении фосфорилирования отдельных STAT-факторов, что, в свою очередь, определяет изменение чувствительности ИКК к цитокинам и формирование стимулов к дифференциации и пролиферации соответствующих популяций ИКК, включая Т-хелперы [9-12, 16, 17] Таким образом, полученные в настоящем исследовании данные, в том числе, свидетельствующие о важной роли JAK/STAT-сигнального пути, а также баланса SOCS2/STAT3 в регуляции саногенеза у реконвалесцентов ВП, позволяют считать указанные факторы потенциальными терапевтическими мишенями, воздействие на которые способно обеспечить усиление активности процессов саногенеза, а также восстановление нарушенной иммунологической реактивности на этапе реабилитации больных, перенесших пневмонию [14,[20][21][22]. При этом очевидно, что восстановление у реконвалесцентов ВП исходной реактивности ИКК определяет нормальное восстановление процессов репарации и регенерации тканей, а также является фактором препятствующих развитию повторных инфекционных заболеваний, в том числе, повторных пневмоний, а также суперинфекций [17].…”