The time-varying electromagnetic field (EMF) has been widely studied as one of the exogenous stimulation methods for improving bone healing. Our previous study showed that osteogenic differentiation of adipose-derived stem cells was accelerated by a 45-Hz EMF, whereas a 7.5-Hz EMF inhibited osteogenic marker expression. Accordingly, we hypothesized that each negative and positive condition for the osteogenic differentiation could inversely influence osteoclast formation and differentiation. Here, we demonstrated that osteoclast formation, differentiation, and activity can be regulated by altering the frequency of the electromagnetic stimulation, such as 7.5 (negative for osteogenic differentiation) and 45 Hz (positive for osteogenic differentiation). A 45 Hz EMF inhibited osteoclast formation whereas a 7.5-Hz EMF induced differentiation and activity. Osteoclastogenic markers, such as NFATc1, TRAP, CTSK, MMP9, and DC-STAMP were highly expressed under the 7.5-Hz EMF, while they were decreased at 45 Hz. We found that the 7.5-Hz EMF directly regulated osteoclast differentiation through ERK and p38 MAPK activation, whereas the EMF at 45 Hz suppressed RANKL-induced phosphorylation of IκB. Additionally, actin ring formation with tubules and bone resorptive activity were enhanced at 7.5 Hz through increased integrin β3 expression. However, these were inhibited at 45 Hz. Although many questions remain unanswered, our study indicates that osteoclast formation and differentiation were controllable using physical tools, such as an EMF. It will now be of great interest to study the ill-defined correlation between electromagnetic conditions and osteoclast activities, which eventually could lead to determining the therapeutic characteristics of an EMF that will treat bone-related diseases.
Keywords: Bone; Electromagnetic field; Frequency; Osteoclast.
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