BIOCHEMICAL PATHWAY MEDIATING THE RESPONSE OF BONE-CELLS TO CAPACITIVE COUPLING

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.