S63845 Living systems are constantly in motion and a

Living systems are constantly in motion, and a changing magnetic field (MF) is associated with a changing electric field (EF). This has been shown via Faraday\’s Law, which states that a MF will interact with an electric circuit to produce an electromotive force. Endogenous pulsed EMF arises from the movement of muscles, tendons, and the actions of the musculoskeletal system (Hastings and Mahmud, 1988). Mechanical deformation of dry bone ex vivo generates piezoelectricity through bending strains associated with spatial gradients of permanent dipoles in collagen molecules. In living bone however, small piezoelectric potentials are shielded (Otter et al., 1998b). In physiology, mechanical stress-generated potentials are formed by mechanisms such as: 1) the streaming potential, which is the electric potential difference between a liquid and a capillary, diaphragm, or porous solid in which the fluid is forced to flow; or 2) the entrainment of ions caused by fluid motion through the bone (Otter et al., 1998b). The EMF caused by either of these reactions is able to penetrate tissue, and the MF component can induce electric currents in the bone or muscle tissue via Faraday coupling. Faraday coupling is a form of inductance by which the current in one system induces a voltage in another. Vibrations of human muscles induce mechanical strains on bone and currents in the range of 5–30Hz frequencies during quiet muscle activity (standing), and <10Hz while walking (Antonsson and Mann, 1985). Bone S63845 have strong frequency selectivity with EMF effectiveness peaking in the range of 15–30Hz. In this range, fields as low as 0.01mV/cm affect remodeling activity (McLeod and Rubin, 1993), and endogenous EMF of 1Hz, with current densities of 0.1–1.0mA/cm2 (Lisi et al., 2006) produced during walking.
Research into this phenomenon found that voltage gradients were not just membrane potentials, but specific signals for key metabolic processes in embryonic development and regenerative wound healing (Hotary and Robinson, 1992; Levin, 2007; Nuccitelli, 2003). These signals lead the way for cells to migrate by forming voltage gradients between the intracellular and extracellular environment (Funk and Monsees, 2006). Voltage gradients are localized direct current EFs which are switched on and off at different developmental stages (McGaig et al., 2005). They spread into the extracellular space, as well as into the cytoplasm of one or more cells, coupled by gap junctions (Funk et al., 2009). These gradients can penetrate the cell membrane, into the cytoplasm, and even the nuclear membrane, through signal transduction, whereby the EMF signal is received via receptors on the cell surface, then processed by G-proteins that couple the receptors to effectors, such as ion channels (Ermakov et al., 2012). These signal transduction processes have been reported to show a correlation between the presence of EMF gradients and cellular response in embryogenesis (Funk and Monsees, 2006; Sundelacruz et al., 2013). For hBMSCs to differentiate, there must be effective exogenous stimuli providing direction for their differentiation capabilities. One such stimuli is sinusoidal low-frequency EMF (0.3–100Hz), which produces fields that are coherent (Adey, 1993), and produce regularly recurring signals — that must be present for a certain minimum duration (Litovitz et al., 1993). This resonant coherence is the key to inducing large effects with low thresholds (Panagopoulos et al., 2002). Conservative estimates show that a 1μV induced membrane potential can be detected after 10ms by fewer than 108 ion channels; therefore a strong EMF is not required. According to several different authors (Jacobson, 1994; Jacobson and Yamanashi, 1995; Sandyk, 1996; Persinger, 2006; Persinger and Koren, 2007), picoTesla–nanoTesla intensity EMF is effective with appropriate resonance as a function of the charge and mass of the target molecule (Jacobson, 1994; Jacobson and Yamanashi, 1995; Persinger, 2006; Persinger and Koren, 2007; Sandyk, 1996).