In vivo experiments have demonstrated (a) that transient electrical potentials are induced in impact-loaded bone, and (b) that bone formation is increased in response to electrical stimulation. Therefore, it has been hypothesized that, in response to mechanical loading, mechanical energy in bone is transduced into biologically relevant electrical energy. In order to study the mechanism through which electric fields may increase bone formation, a model system was developed were bone cells or bone organ cultures were exposed to a capacitively-coupled electric field of low frequency (8-25 Hz) and extremely low amplitude (estimated 10-7 V/cm in the culture medium) for 30 minutes.
Using this model system it was found that alkaline phosphatase rich (ie; more differentiated) calvarial cells exhibited a frequency-dependent increase in both release of mitogen activity into the culture medium and cell proliferation with a maximum effect occuring at 16 Hz. Furthermore, it was found that electric field-stimulated calvarial cell proliferation was dependent on acute release of mitogen activity into the culture medium. In addition, this acute electric field-stimulated release of mitogen activity was independent of de novo protein synthesis but could be blocked by a calmodulin antagonist.
The effect of electric field-exposure on bone organ cultures was also examined. Similiar to the effect on cell cultures, it was found that electric field exposure increased both the release of mitogen activity and bone cell proliferation in embryonic chick tibiae. Electric field exposure also increased bone matrix formation in these embryonic chick tiabiae. Interestingly, it was found that a 30 min/d exposure increased bone matrix formation to a greater extent than the increase from a constant exposure.
The following hypothesis was constructed to account for the observed effects of electric field-exposure on skeletal tissue. First, electric field-exposure stimulates the release of a pre-synthesized mitogen (possibly from plasma membrane-associated vesicles) from differentiated (ie; osteoblastic) bone cells in a Ca/calmodulin dependent manner. The mitogen(s) thus released then act on less differentiated bone cells to increase the rate of cell proliferation. This response was associated with increased phosphorylation of proteins and lipids in the target cells. The increase in cell proliferation results in an increase in bone cell number, which, in turn, results in increased bone matrix formation.
John Randolph Farley
William Ross Adey
Kin-Hing William Lau
E. Clifford Hermann
Doctor of Philosophy (PhD)
Year Degree Awarded
Date (Title Page)
Library of Congress/MESH Subject Headings
Bone Development; Electromagnetics -- therapeutic use; Growth Substances
Loma Linda University Libraries
This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.
Fitzsimmons, Robert James, "The Effects of Exposure to Extremely Low-Amplitude, Low-Frequency Electric Fields on Skeletal Tissue, In Vitro" (1998). Loma Linda University Electronic Theses, Dissertations & Projects. 860.
Loma Linda University Electronic Theses and Dissertations
Loma Linda University. Del E. Webb Memorial Library. University Archives