Regulation of transforming growth factor-beta (TGF-beta) gene expression in living cells via the application of specific and selective electric and electromagnetic fields

A method for treating a bone fracture, fracture at risk, delayed union, nonunion, bone defect, spine fusion, osteonecrosis, osteoporosis, and/or other conditions in which Transforming Growth Factor (TGF)-β1, β2, and/or β3 protein has been implicated in a patient, comprising the steps of:

• a. generating at least one specific and selective electric signal that when applied to electrodes, one or more coils, or other field generating devices operatively disposed with respect to targeted tissue causes the generation of a specific and selective electric field in the targeted tissue that substantially up-regulates the gene expression of TGF-β1, β2, and/or β3 protein in said targeted tissue as measured by mRNA;
• and
• b. exposing said targeted tissue to the specific and selective electric field generated by said electrodes, one or more coils, or other field generating devices upon application of said at least one specific and selective electric signal thereto for a predetermined duration of time at predetermined intervals so as to selectively up-regulate the gene expression of TGF-β 1, β2, and/or β3 protein in said targeted tissue as measured by mRNA.

A device for the treatment of a bone fracture, fracture at risk, delayed union, nonunion, bone defect, spine fusion, osteonecrosis, osteoporosis, and/or other conditions in which Transforming Growth Factor (TGF)-β1, β2, and/or β3 protein has been implicated in a patient, comprising a signal source that generates at least one specific and selective electric signal and electrodes, one or more coils, or other field generating devices that are operatively disposed with respect to targeted tissue, said electrodes, one or more coils, or other field generating devices upon receipt of said at least one specific and selective electric signal causing the generation of a specific and selective electric field in the targeted tissue that substantially up-regulates the gene expression of TGF-β1, β2, and/or β3 protein in said targeted tissue as measured by mRNA upon application of said at least one specific and selective electric field thereto for a predetermined duration of time at predetermined intervals.

A method of determining a specific and selective electric signal that when applied to an electrode, one or more coils or other field generating device causes the generation of an electric field in targeted tissue that up-regulates Transforming Growth Factor (TGF)-β1, β2, and/or β3 protein in the targeted tissue, comprising the steps of starting with a starting electric signal with a signal shape and frequency that when applied to said electrodes, one or more coils, or other field generating devices generates an electric field that is known or thought to affect cellular production of TGF-β1, β2, and/or β3 protein, selectively varying a duration of application of said starting signal until a duration that provides a most significant increase in production of TGF-β1, β2, and/or β3 protein is found, selectively varying an amplitude of the starting signal until an amplitude that provides a most significant increase in production of TGF-β1, β2, and/or β3 protein is found, selectively varying a duty cycle of the starting signal until a duty cycle that provides a most significant increase in production of TGF-β1, β2, and/or β3 protein is found, and selectively varying an on-off interval of the duty cycle of the signal until an on-off interval that provides a most significant increase in production of TGF-β1, β2, and/or β3 protein is found.