Exposure to Extremely Low-Frequency Pulsed Electromagnetic Fields Promotes Fracture Healing through Alleviating the Damage Caused by Cigarette Smoke and Modulating the Osteoimmune Microenvironment

Abstract

The etiology and progression of osteoporosis are multifactorial and still not fully understood. With the development of evidence-based medicine and pathophysiology, the treatment for promoting new bone formation and restoring the health of bone has gradually developed into a multidisciplinary and comprehensive treatment. In this project, we proved that the use of ELF-PEMF as a treatment for promoting new bone formation and preventing fracture non-union is effective and feasible. Our data indicated that the daily exposure of specific ELF-PEMF was able to directly increase the cell viability, migration, spreading, and adhesion of SCP-1 cells. The molecular mechanism is that ELF-PEMF activated the TGF-β signaling pathway, and protected the structure and function of the primary cilia of SCP-1 cells. Moreover, we found that the daily intermittent exposure (10 min every 8 h) is even better than the daily continuous exposure (30 min every 24 h) in improving cell viability. Interestingly, we found that piezo1 played an important role in the ELF-PEMF treatment. The gene expression of piezo1 increased after the intermittent exposure, and the function of piezo1 was activated thus leading to calcium influx into SCP-1 cells. In contrast, treating cells with piezo1 inhibitor Dooku1 blocked the function of piezo1 and impaired the mineral deposition. Therefore, ELF-PEMF can directly promote fracture healing. Nevertheless, we also found that ELF-PEMF with specific parameters can modulate the activity of macrophages to indirectly affect the osteogenesis of SCP-1 cells, e.g., field A induced the pro-inflammatory activity of macrophages, and field B induced the anti-inflammatory activity of macrophages, and enhanced the ECM formation of SCP-1 cells on the early stage. Taken together, ELF-PEMF exposure can, directly and indirectly, promote the healing process and might be a useful tool in critical bone healing such as Pseudarthrosis.