Electromagnetic fields promote osteogenesis of rat mesenchymal stem cells through the PKA and ERK1/2 pathways

J Tissue Eng Regen Med. 2016 Oct;10(10):E537-E545. doi: 10.1002/term.1864. Epub 2014 Mar 16.

Abstract

It has been reported that electromagnetic fields (EMFs) can promote the healing of non-union, osteogenesis and differentiation of the osteoblasts. However, its mechanism has not been unravelled. In this study, we detected some response induced by EMF and evaluated the importance of these signals for EMF-induced osteogenesis in bone marrow mesenchymal stem cells (MSCs). We characterized the expression of EMF-induced osteogenesis markers in MSCs, using RT-PCR and real-time PCR. Western blot was used to detect the signalling pathways. We found that EMF could promote osteogenesis in MSCs, along with the expression of several osteogenic markers. EMF-induced cyclic adenosine monophosphate (cAMP) level increase causes protein kinase A (PKA) and extracellular signal-regulated kinase (ERK)1/2 phosphorylation. Pretreating the MSCs with the mitogen-activated protein kinase (MAPK)/ERK kinase 1/2 (MEK1/2) inhibitor PD98059, or the PKA inhibitor H-89, significantly inhibited the induction of osteogenic markers, showing that EMF induction of osteogenesis was dependent on the ERK and PKA signalling pathways. Therefore, our study showed that EMF promoted MSC osteogenesis and that the EMF-induced osteogenic markers were mediated by both the PKA and MAPK signalling pathways. Copyright © 2014 John Wiley & Sons, Ltd.

Keywords: ERK1/2; MSCs; cAMP; electromagnetic fields (EMF); osteogenesis; protein kinase A (PKA).

MeSH terms

  • Animals
  • Antigens, Differentiation / biosynthesis
  • Antigens, Differentiation / genetics
  • Cyclic AMP / genetics
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Electromagnetic Fields*
  • Flavonoids / pharmacology
  • Isoquinolines / pharmacology
  • MAP Kinase Signaling System*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Osteogenesis*
  • Rats
  • Rats, Sprague-Dawley
  • Sulfonamides / pharmacology

Substances

  • Antigens, Differentiation
  • Flavonoids
  • Isoquinolines
  • Sulfonamides
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 3
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one