Pulsed electromagnetic fields rapidly modulate intracellular signaling events in osteoblastic cells: comparison to parathyroid hormone and insulin.
Pulsed electromagnetic field (PEMF) devices are approved for the healing of bone nonunions, but there is a lack of understanding as to their mechanism of action at the cell and molecular level. Intermittent parathyroid hormone (PTH) therapy is currently utilized for treatment of osteoporosis, and is also being investigated for the purpose of augmenting fracture healing. Insulin and IGF-1 are also thought to play important anabolic roles in osteogenesis. In this report, signaling pathways activated by acute PTH or insulin treatments were compared to those activated by PEMF treatment in osteoblast-like cells. Some signaling molecules like the extracellular response kinases 1/2 (Erk1/2) and the cAMP response element binding protein (CREB) were activated by insulin and PTH, respectively, but not by PEMF treatment. Other signaling molecules like the insulin receptor substrate-1 (IRS-1), the S6 ribosomal subunit kinase, and the endothelial nitric oxide synthase (eNOS) were phosphorylated by PTH, insulin, and PEMF to the same relative extent and within the same time frame. IRS-1, eNOS, and S6 have been implicated in bone anabolism, and our results suggest that the anabolic effects of PEMF may be mediated, in part, through the activation of these proteins.
Schnoke
Matthew
M
Department of Biomedical Engineering and The Orthopaedic Research Center, Lerner Research Institute, ND20, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
Midura
Ronald J
RJ
D045930:Anabolic Agents / Q000494:pharmacology*; D000818:Animals; D050882:CREB-Binding Protein / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D002460:Cell Line; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D010766:Phosphorylation; D011827:Radiation; D011878:Radiotherapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D019893:Ribosomal Protein S6 Kinases / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects*
D045930:Anabolic Agents; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010281:Parathyroid Hormone; D010750:Phosphoproteins; D052250:Nitric Oxide Synthase Type III; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat; D019893:Ribosomal Protein S6 Kinases; D048052:Mitogen-Activated Protein Kinase 3