Pulsed electromagnetic field stimulation of MG63 osteoblast‐like cells affects differentiation and local factor production

Abstract

Pulsed electromagnetic field stimulation has been used to promote the healing of chronic nonunions and fractures with delayed healing, but relatively little is known about its effects on osteogenic cells or the mechanisms involved. The purpose of this study was to examine the response of osteoblast-like cells to a pulsed electromagnetic field signal used clinically and to determine if the signal modulates the production of autocrine factors associated with differentiation. Confluent cultures of MG63 human osteoblast-like cells were placed between Helmholtz coils and exposed to a pulsed electromagnetic signal consisting of a burst of 20 pulses repeating at 15 Hz for 8 hours per day for 1, 2, or 4 days. Controls were cultured under identical conditions, but no signal was applied. Treated and control cultures were alternated between two comparable incubators and, therefore, between active coils; measurement of the temperature of the incubators and the culture medium indicated that application of the signal did not generate heat above the level found in the control incubator or culture medium. The pulsed electromagnetic signal caused a reduction in cell proliferation on the basis of cell number and [3H]thymidine incorporation. Cellular alkaline phosphatase-specific activity increased in the cultures exposed to the signal, with maximum effects at day 1. In contrast, enzyme activity in the cell-layer lysates, which included alkaline phosphatase-enriched extracellular matrix vesicles, continued to increase with the time of exposure to the signal. After 1 and 2 days of exposure, collagen synthesis and osteocalcin production were greater than in the control cultures. Prostaglandin E2 in the treated cultures was significantly reduced at 1 and 2 days, whereas transforming growth factor-beta1 was increased; at 4 days of treatment, however, the levels of both local factors were similar to those in the controls. The results indicate enhanced differentiation as the net effect of pulsed electromagnetic fields on osteoblasts, as evidenced by decreased proliferation and increased alkaline phosphatase-specific activity, osteocalcin synthesis, and collagen production. Pulsed electromagnetic field stimulation appears to promote the production of matrix vesicles on the basis of higher levels of alkaline phosphatase at 4 days in the cell layers than in the isolated cells, commensurate with osteogenic differentiation in response to transforming growth factor-beta1. The results indicate that osteoblasts are sensitive to pulsed electromagnetic field stimulation, which alters cell activity through changes in local factor production.

Upregulation of basal TGFβ1 levels by EMF coincident with chondrogenesis – implications for skeletal repair and tissue engineering

“…Three groups have demonstrated increases in the transcription of mRNA for several BMP in skeletal tissue with EMF exposure [7,37,51]. Increases in the transcription of TGFP mRNA suggest that the stimulation of TGFP expression may be a mechanism through which physical agents affect complex tissue behavior such as cell differentiation and through which the effects of EMF may be amplified [25,32,52]. Physical agents may be synergistic with endogenous synthesized, or exogenously applied, growth factors in repair.…”

Electrical stimulation therapies for spinal fusions: current concepts

“…Most investigations on the mechanism of action of IC technology have been performed with the PEMF signal which is FDA approved for fracture healing but not spinal fusion [1,4,8,11,29,43,44,51,64]. There is only one study using the PEMF signal that is clinically approved for spinal fusions [61] and a few studies with CMF [11,20,21,58].…”

Exposure of mouse preosteoblasts to pulsed electromagnetic fields reduces the amount of mature, type I collagen in the extracellular matrix

“…In addition, contradictory results have been reported. For example, cell proliferation, as assayed by cell number and 3 H-thymidine incorporation, have been reported to increase, 6 decrease, 15 and remain unaffected 15 by PEMF exposure. Similarly, the production of alkaline phosphatase has been reported to either increase 15,16 or decrease 17 following PEMF exposure.…”

“…For example, PEMF exposure has been associated with increases in Type I collagen, alkaline phosphatase, 7,13,15,16 total extracellular matrix, 18 and glycosaminoglycans. 19,20 However, it is not known if these changes are primary or secondary effects of PEMF exposure.…”