Dg. Lorich et al., BIOCHEMICAL PATHWAY MEDIATING THE RESPONSE OF BONE-CELLS TO CAPACITIVE COUPLING, Clinical orthopaedics and related research, (350), 1998, pp. 246-256
Rat calvarial bone cells or mouse MC3T3-E1 bone cells subjected to a c
apacitively coupled electric field of 20 mV/cm consistently showed sig
nificant increases in cellular proliferation as determined by deoxyrib
onucleic acid content. Verapamil, a membrane calcium channel blocker;
W-7, a calmodulin antagonist; indocin, a prostaglandin synthesis inhib
itor; or bromophenacyl bromide, a phospholipase A(2), inhibitor, each
at a concentration that did not interfere with cell proliferation in c
ontrol cultures, inhibited proliferation in those cultures subjected t
o the electric field. In contrast, neomycin, an inhibitor of the inosi
tol phosphate cascade, did not inhibit this electrically induced cellu
lar proliferation. Prostaglandin E-2 production also was increased sig
nificantly with electrical stimulation, and this increase was inhibite
d by verapamil or indocin but not by neomycin. Thus, the data suggest
that the signal transduction mediating the proliferative response of c
ultured bone cells to a capacitively coupled field involved transmembr
ane calcium translocation via voltage gated calcium channels, activati
on of phospholipase A(2),, and a subsequent increase in prostaglandin
E-2.,, Increases in cytosolic calcium and activated calmodulin are imp
lied. The inositol phosphate pathway; unlike its dominant role in sign
al transduction in mechanically stimulated bone cells, does not appear
to play a role in signal transduction in the proliferative response o
f bone cells to electrical stimulation.