Ch. Lohmann et al., Pulsed electromagnetic field stimulation of MG63 osteoblast-like cells affects differentiation and local factor production, J ORTHOP R, 18(4), 2000, pp. 637-646
Pulsed electromagnetic field stimulation has been used to promote the heali
ng of chronic nonunions and fractures with delayed healing, but relatively
little is known about its effects on osteogenic cells or the mechanisms inv
olved. 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 assoc
iated with differentiation. Confluent cultures of MG63 human osteoblast-lik
e cells were placed between Helmholtz coils and exposed to a pulsed electro
magnetic 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 al
ternated between two comparable incubators and, therefore, between active c
oils; measurement of the temperature of the incubators and the culture medi
um indicated that application of the signal did not generate heat above the
level found in the control incubator or culture medium. The pulsed electro
magnetic signal caused a reduction in cell proliferation on the basis of ee
l number and [H-3] thymidine incorporation. Cellular alkaline phosphatase-s
pecific activity increased in the cultures exposed to the signal, with maxi
mum effects at day 1. In contrast, enzyme activity in the eel-layer lysates
, which included alkaline phosphatase-enriched extracellular matrix vesicle
s, continued to increase with the time of exposure to the signal. After 1 a
nd 2 days of exposure, collagen synthesis and osteocalcin production were g
reater than in the control cultures. Prostaglandin E-2 in the treated cultu
res was significantly reduced at 1 and 2 days, whereas transforming growth
factor-beta 1 was increased; at 4 days of treatment, however, the levels of
both local factors were similar to those in the controls. The results indi
cate enhanced differentiation as the net effect of pulsed electromagnetic f
ields on osteoblasts, as evidenced by decreased proliferation and increased
alkaline phosphatase-specific activity, osteocalcin synthesis, and collage
n production. Pulsed electromagnetic field stimulation appears to promote t
he 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, commen
surate with osteogenic differentiation in response to transforming growth f
actor-beta 1. The results indicate that osteoblasts are sensitive to pulsed
electromagnetic field stimulation, which alters cell activity through chan
ges in local factor production.