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. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:933–940, 2007