Osteoprotegerin (OPG) Production by Cells in the Osteoblast Lineage is Regulated by Pulsed Electromagnetic Fields in Cultures Grown on Calcium Phosphate Substrates

Abstract

Pulsed electromagnetic fields (PEMF) used clinically to stimulate bone formation enhance the osteogenic effects of BMP-2 on human mesenchymal stem cells (MSCs) if the MSCs are grown in osteogenic medium and are cultured on calcium phosphate (CaP) surfaces rather than tissue culture polystyrene plastic (TCPS). This study tested if PEMF's effects on cells in the osteoblast lineage are substrate dependent and if factors produced by osteoblasts that regulate osteoclastic bone resorption, might also be regulated by PEMF. Human MSCs treated with BMP-2 and human osteoblast-like cells (normal human osteoblasts [NHOst cells], MG63 cells, SaOS-2 cells) were cultured on CaP or TCPS and their response to PEMF (4.5 ms bursts of 20 pulses repeating at 15 Hz for 8 h/day) determined as a function of decoy receptor osteoprotegerin (OPG) and RANK ligand (RANKL) production, both of which are associated with regulation of osteoclast differentiation. The results showed that when osteoblast-like cells were cultured on CaP, PEMF decreased cell number and increased production of paracrine factors associated with reduced bone resorption like OPG. RANKL was unaffected, indicating that the OPG/RANKL ratio was increased, further supporting a surface-dependent osteogenic effect of PEMF. Moreover, effects of estrogen were surface dependent and enhanced by PEMF, demonstrating that PEMF can modulate osteogenic responses to anabolic regulators of osteoblast function. These effects of PEMF would not be evident in models examining cells in traditional culture on plastic.