Effects of Electromagnetic Fields in Experimental Fracture Repair

Otter, Mark W.; McLeod, Kenneth J.; Rubin, Clinton T.

doi:10.1097/00003086-199810001-00011

Cited by 97 publications

(52 citation statements)

References 96 publications

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“…Importantly, it has been claimed that electromagnetic fields can exert biological effects (19)(20)(21)(22). In addition, recent theoretical (16) and experimental (15) work suggests a possible mechanism whereby an electric field can alter an enzymecatalyzed reaction.…”

Section: Discussionmentioning

confidence: 99%

Noise-based switches and amplifiers for gene expression

Hasty

Pradines

Dolnik

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

575

499

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The regulation of cellular function is often controlled at the level of gene transcription. Such genetic regulation usually consists of interacting networks, whereby gene products from a single network can act to control their own expression or the production of protein in another network. Engineered control of cellular function through the design and manipulation of such networks lies within the constraints of current technology. Here we develop a model describing the regulation of gene expression and elucidate the effects of noise on the formulation. We consider a single network derived from bacteriophage and construct a two-parameter deterministic model describing the temporal evolution of the concentration of repressor protein. Bistability in the steady-state protein concentration arises naturally, and we show how the bistable regime is enhanced with the addition of the first operator site in the promotor region. We then show how additive and multiplicative external noise can be used to regulate expression. In the additive case, we demonstrate the utility of such control through the construction of a protein switch, whereby protein production is turned ''on'' and ''off'' by using short noise pulses. In the multiplicative case, we show that small deviations in the transcription rate can lead to large fluctuations in the production of protein, and we describe how these fluctuations can be used to amplify protein production significantly. These results suggest that an external noise source could be used as a switch and͞or amplifier for gene expression. Such a development could have important implications for gene therapy.R egulated gene expression is the process through which cells control fundamental functions such as the production of enzymatic and structural proteins and the time sequence of this production during development (1, 2). Many of these regulatory processes take place at the level of gene transcription (3), and there is evidence that the underlying reactions governing transcription can be affected by external influences from the environment (4).Because experimental techniques are increasingly capable of providing reliable data pertaining to gene regulation, theoretical models are becoming important in the understanding and manipulation of such processes. The most common theoretical approach is to model the interactions of elements in a regulatory network as biochemical reactions. Given such a set of chemical reactions, the individual jump processes (i.e., the creation or destruction of a given reaction species) and their associated probabilities are considered. In its most general form, this approach often leads to a type of Monte Carlo simulation of the interaction probabilities (5). Although this approach suffers from a lack of analytic tractability, its strength is its completeness-fluctuations in species' concentrations are embedded in the modeling process. These internal fluctuations are important for systems containing modest numbers of elements, or when the volume is small.Rate equations or...

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Section: Discussionmentioning

confidence: 99%

Noise-based switches and amplifiers for gene expression

Hasty

Pradines

Dolnik

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

575

499

View full text Add to dashboard Cite

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“…Clinical application of electromagnetic fields arose from the discovery that time-varying electric fields are generated in living bone deformed by mechanical loads. 1 The application of pulsed electromagnetic fields (PEMF) appears to affect differentiation of chondrocytes 2 and already differentiated bone cells through various transduction pathways and growth factors, 1,3 and decreasing osteoclastic resorption and increasing osteoblastic bone formation. [4][5][6][7][8] Clinical and laboratory trials have shown a positive effect in the healing of acute fracture, 9,10 delayed and nonunion, 9,[11][12][13][14] congenital pseudarthosis, [15][16][17] failed arthrodesis, 18,19 and to decrease or reverse osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

Effect of pulsed electromagnetic fields on maturation of regenerate bone in a rabbit limb lengthening model

BARONE¹,

Sbordone

Ramaglia

2005

Journal Orthopaedic Research

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ABSTRACT:To study the effect of applying pulsed electromagnetic fields (PEMF) during the consolidation phase of limb lengthening, a mid-tibial osteotomy was performed in 18 adult New Zealand White rabbits and an external fixator was applied anteromedially. Animals were randomly assigned to treatment and control groups. After a 7-day latency period, the tibiae were distracted 0.5 mm every 12 h for 10 days. The treatment group received a 20-day course of PEMF for 60 min daily, coinciding with initiation of the consolidation phase. The control group received sham PEMF. Radiographs were performed weekly after distraction. Animals were euthanized 3 weeks after the end of distraction. Radiographic analysis revealed no significant difference in regenerate callus area between treatment and control tibiae immediately after distraction, at 1 week, 2 weeks, or 3 weeks after distraction ( p ¼ 0.71, 0.22, 0.44, and 0.50, respectively). There was also no significant difference in percent callus mineralization ( p ¼ 0.96, 0.69, 0.99, and 0.99, respectively). There was no significant difference between groups with respect to structural stiffness ( p ¼ 0.80) or maximal torque to failure ( p ¼ 0.62). However, there was a significant positive difference in mineral apposition rate between groups during the interval 1-2 weeks post-distraction ( p < 0.05). This difference was no longer evident by the interval 2-3 weeks post-distraction. While PEMF applied during the consolidation phase of limb lengthening did not appear to have a positive effect on bone regenerate, it increased osteoblastic activity in the cortical bone adjacent to the distraction site. Since the same PEMF signal was reported to be beneficial in the rabbit distraction osteogenesis when applied during distraction phase and consolidation phase, application of PEMF in the early phase may be more effective. Further work is necessary to determine optimal timing of the PEMF stimulation during distraction osteogenesis. ß

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“…The frequency spectra of these waveforms, however, can range from 1 Hz to greater than 1 MHz. 34 Thus, the significance of the association, but the weak overall relationships, encourage extension of the analysis to PEMF characteristics expressed in the frequency-amplitude domain. Analysis and reduction of the waveform frequency spectra to a statistically manageable number of independent variables may improve upon the present results, which accounted for less than 20% of the shared variance in the a1(I) collagen.…”

Section: Discussionmentioning

confidence: 99%

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

Sakai

Patterson

Ibiwoye

et al. 2005

Journal Orthopaedic Research

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We tested the hypothesis that exposure of a mouse preosteoblast cell line to pulsed electromagnetic fields (PEMF) would affect components of the extracellular matrix. We report that exposure of MC3T3-E1 cells to a single PEMF waveform significantly reduced the amount of mature, a1(I) collagen in the extracellular matrix (ECM) and the conditioned medium, without affecting the amount of total ECM protein. This decrease was not due to changes in the steady-state level of Col1A1 mRNA or to degradation of mature collagen. We then tested the effect of three distinct PEMF waveforms, two orthogonal coil orientations, and two waveform amplitude levels on the amount of a1(I) collagen in the conditioned medium. A sequence of factorial ANOVAs and stepwise regression modeling revealed that the period (duration) of the individual pulses accounted for a significant proportion of the variance associated with the amount of a1(I) collagen in the conditioned medium. The total variance accounted for, however, was small (R 2 ¼ 0.155, p < 0.001 and R 2 ¼ 0.172, p < 0.001, in the horizontal and vertical orientations, respectively). The positive and negative regression coefficients for the coil orientations revealed that the influence of pulse period was significantly different for the orthogonal coil orientations (p < 0.001). The findings imply that the dominant influence of PEMF on the amount of mature, a1(I) collagen in the ECM is related to variables other than those expressed in the time-amplitude domain. The results provide objective direction toward identifying waveform characteristics that contribute to the observed between-waveform differences with regard to collagen. Advances in this area may lead toward improving waveforms and waveform delivery protocols. ß

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Effects of Electromagnetic Fields in Experimental Fracture Repair

Cited by 97 publications

References 96 publications

Noise-based switches and amplifiers for gene expression

Noise-based switches and amplifiers for gene expression

Effect of pulsed electromagnetic fields on maturation of regenerate bone in a rabbit limb lengthening model

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

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