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Purpose: For many years, our laboratory has been investigating different biological substrates for the effects of electromagnetic stimulation proposed in orthopaedic treatments. The results show an acceleration of differentiation at the expense of proliferation. This study using microarray analysis is focused on the cellular mechanisms involved., Methods: A microarray analysis (Affymetrix) allowing the screening of the expression of 38,500 genes was used on epidermal cells sampled from three different human donors and distributed within each donor in seven groups of 12 explants, stimulated at different times, to compare control. Modifications of the expression of BMP-2, 4 and 7 were studied at days four, seven and 12., Results: The expression of BMP-2 was significantly increased at day 12 on the stimulated samples. J(4) and J(7) did not show any significant difference nor did the expression of BMP-4 and 7 at the different times., Conclusion: The results obtained in previous experiments on cellular substrates, bone embryonic tissue and clinical series were all consistent with the increase of BMP-2. Other publications have confirmed an increase of BMP-2 under electric or electromagnetic stimulation. The increase of BMP-2 appears as an effect of the electromagnetic field stimulations applied in orthopaedics. This observation contributes towards possible indications and a better understanding of the cellular mechanism.

An acceleration of differentiation, at the expense of proliferation, is observed after exposure of various biological models to low frequency and low amplitude electric and electromagnetic fields. Following these results showing significant modifications, we try to identify the biological mechanism involved at the cell level through microarray screening. For this study, we use epidermis cultures harvested from human abdominoplasty. Two platinum electrodes are used to apply the electric signal. The gene expressions of 38,500 well-characterized human genes are analyzed using Affymetrix(®) microarray U133 Plus 2.0 chips. The protocol is repeated on three different patients. After three periods of exposure, a total of 24 chips have been processed. After the application of ELF electric fields, the microarray analysis confirms a modification of the gene expression of epidermis cells. Particularly, four up-regulated genes (DKK1, TXNRD1, ATF3, and MME) and one down-regulated gene (MACF1) are involved in the regulation of proliferation and differentiation. Expression of these five genes was also confirmed by real-time rtPCR in all samples used for microarray analysis. These results corroborate an acceleration of cell differentiation at the expense of cell proliferation., (© 2010 Wiley-Liss, Inc.)

The effects of low frequency pulsed electrical current on epidermal repair in vitro were examined. Charge-balance current stimuli proposed for chronic wound treatment were tested on skin keratinocytes cultured at an air-liquid interface on dead human dermis. Results imply that the balance between proliferation and differentiation in electrically treated samples is significantly modified in favor of differentiation. More advanced differentiation, shown through epidermal histology, was obtained in cultures exposed to electrical current, whereas the culture growth, the result of keratinocyte migration and proliferation, was greater in control samples.