Biochemical pathway mediating the response of bone cells to capacitive coupling.
Rat calvarial bone cells or mouse MC3T3-E1 bone cells subjected to a capacitively coupled electric field of 20 mV/cm consistently showed significant increases in cellular proliferation as determined by deoxyribonucleic acid content. Verapamil, a membrane calcium channel blocker; W-7, a calmodulin antagonist; indocin, a prostaglandin synthesis inhibitor; or bromophenacyl bromide, a phospholipase A2 inhibitor, each at a concentration that did not interfere with cell proliferation in control cultures, inhibited proliferation in those cultures subjected to the electric field. In contrast, neomycin, an inhibitor of the inositol phosphate cascade, did not inhibit this electrically induced cellular proliferation. Prostaglandin E2 production also was increased significantly with electrical stimulation, and this increase was inhibited by verapamil or indocin but not by neomycin. Thus, the data suggest that the signal transduction mediating the proliferative response of cultured bone cells to a capacitively coupled field involved transmembrane calcium translocation via voltage gated calcium channels, activation of phospholipase A2, and a subsequent increase in prostaglandin E2. Increases in cytosolic calcium and activated calmodulin are implied. The inositol phosphate pathway, unlike its dominant role in signal transduction in mechanically stimulated bone cells, does not appear to play a role in signal transduction in the proliferative response of bone cells to electrical stimulation.
Lorich
D G
DG
McKay Laboratory of Orthopaedic Research, Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, Philadelphia, USA.
Brighton
C T
CT
Gupta
R
R
Corsetti
J R
JR
Levine
S E
SE
Gelb
I D
ID
Seldes
R
R
Pollack
S R
SR
D000818:Animals; D001842:Bone and Bones / Q000166:cytology*; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D004553:Electric Conductivity; D007295:Inositol Phosphates; D051379:Mice; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D013314:Stress, Mechanical
D007295:Inositol Phosphates