Lorich D G, Brighton C T, Gupta R, Corsetti J R, Levine S E, Gelb I D, Seldes R, Pollack S R
McKay Laboratory of Orthopaedic Research, Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, Philadelphia, USA.
Clin Orthop Relat Res. 1998 May(350):246-56.
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.
经20mV/cm电容耦合电场处理的大鼠颅骨细胞或小鼠MC3T3-E1骨细胞，通过脱氧核糖核酸含量测定发现其细胞增殖持续显著增加。维拉帕米（一种膜钙通道阻滞剂）、W-7（一种钙调蛋白拮抗剂）、吲哚美辛（一种前列腺素合成抑制剂）或溴苯酰溴（一种磷脂酶A2抑制剂），每种药物在不干扰对照培养物中细胞增殖的浓度下，均抑制了经电场处理的培养物中的细胞增殖。相比之下，新霉素（一种肌醇磷酸级联反应抑制剂）并未抑制这种电诱导的细胞增殖。电刺激还显著增加了前列腺素E2的产生，这种增加被维拉帕米或吲哚美辛抑制，但未被新霉素抑制。因此，数据表明，介导培养的骨细胞对电容耦合场增殖反应的信号转导涉及通过电压门控钙通道的跨膜钙转运、磷脂酶A2的激活以及随后前列腺素E2的增加。这意味着细胞溶质钙和激活的钙调蛋白增加。肌醇磷酸途径与它在机械刺激的骨细胞信号转导中的主导作用不同，似乎在骨细胞对电刺激的增殖反应的信号转导中不起作用。
