Pulsed electromagnetic fields inhibit osteoclast differentiation in RAW264.7 macrophages via suppression of the protein kinase B/mammalian target of rapamycin signaling pathway

Abstract

When bone resorption, aided by the activity of osteoclasts, exceeds bone formation induced by osteoblasts, bone metabolism loses equilibration, which results in the development of bone diseases, including osteoporosis. Pulsed electromagnetic fields (PEMFs) are known to be involved in various biological processes, including cell proliferation, differentiation and apoptosis. However, the exact mechanism of action of osteoclasts remains poorly understood. In the present study, the effects of PEMFs on osteoclast differentiation and associated signaling pathways were systematically investigated in RAW264.7 macrophages. RAW264.7 cells were induced by receptor activator of nuclear factor‑κB ligand (RANKL) to obtain osteoclasts in vitro. The results of the present study demonstrated that PEMF exposure decreased osteoclast formation, limited tartrate‑resistant acid phosphatase activity, contracted bone resorption area and inhibited osteoclastic specific gene and protein expression. Furthermore, western blot analysis indicated that PEMFs distinctly abolished the upregulation of phosphorylated‑protein kinase B (Akt), ‑mammalian target of rapamycin (mTOR) and ‑ribosome S6 protein kinase (p70S6K) induced by RANKL, which was consistent with the effects of pharmacological inhibitor perifosine and rapamycin. Therefore, the present study suggested that PEMFs reduced osteoclast formation from RAW264.7 macrophages via inhibition of the Akt/mTOR signaling pathway. These findings provided novel insight into the mechanisms through which PEMFs suppress osteoclast differentiation.

Translational Insights into Extremely Low Frequency Pulsed Electromagnetic Fields (ELF-PEMFs) for Bone Regeneration after Trauma and Orthopedic Surgery

“…By inducing ROS, ELF-PEMF thus may favor osteoclastogenesis, an assumption supported by the studies of Pi and Zhang [64,65]. However, there are also several other reports showing ELF-PEMF inhibitory effects on osteoclastogenesis [66][67][68]. He et al suggest that ELF-PEMF suppressive effects are mediated by endocrine effects of osteoblasts [67], a hypothesis supported by several other studies [61,[69][70][71][72].…”

Interleukin‑1 induces receptor activator of nuclear factor‑κB ligand‑independent osteoclast differentiation in RAW264.7 cells

“…Normally, dentine or bone slices are used to evaluate osteoclast differentiation and function (20,43), however, they are difficult to handle and easily damaged. The Corning Osteo Assay Surface represents a convenient and reproducible substitute for slices (26,27).…”

The Possible Role of Electrical Stimulation in Osteoporosis: A Narrative Review

“…Ying Pi et al found that a low-frequency PEMF inhibits osteoclast differentiation by scavenging reactive oxygen species, and it is a potential treatment for osteoporosis [ 60 ]. Yutian Lei et al found that PEMFs inhibit osteoclast differentiation and inhibit the progression of osteoporosis by regulating the Akt/mTOR signaling pathway [ 61 ]. Moreover, many other researchers have found that PEMFs inhibit the progression of osteoporosis by inhibiting osteoclast formation and differentiation [ 62 , 63 , 64 , 65 , 66 ].…”