The simultaneous downregulation of TRPM7 and MagT1 in human mesenchymal stem cells in vitro: Effects on growth and osteogenic differentiation

Biochem Biophys Res Commun. 2019 May 21;513(1):159-165. doi: 10.1016/j.bbrc.2019.03.178. Epub 2019 Apr 2.

Abstract

The magnesium transporters TRPM7 and MagT1 are overexpressed in osteoblastogenesis. We have shown that silencing either TRPM7 or MagT1 accelerates the osteogenic differentiation of human bone mesenchymal stem cells. Here we demonstrate that the simultaneous downregulation of TRPM7 and MagT1 inhibits cell growth and activates autophagy, which is required in the early phases of osteoblastogenesis. In TRPM7/MagT1 downregulating cells the expression of two transcription factors required for activating osteogenesis, i.e. RUNX2 and OSTERIX, is induced more than in the controls both in the presence and in the absence of osteogenic stimuli, while COL1A1 is upregulated in co-silencing cells as much as in the controls. This explains why we found no differences in calcium deposition. We conclude that one of the two transporters should be expressed to accelerate osteogenic differentiation.

Keywords: Autophagy; MagT1; Mesenchymal stem cells; Osteogenic differentiation; TRPM7.

MeSH terms

  • Adult
  • Autophagy
  • Cation Transport Proteins / genetics*
  • Cation Transport Proteins / metabolism
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Down-Regulation
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Osteogenesis
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • RNA Interference
  • TRPM Cation Channels / genetics*
  • TRPM Cation Channels / metabolism

Substances

  • Cation Transport Proteins
  • MagT1 protein, human
  • TRPM Cation Channels
  • Protein Serine-Threonine Kinases
  • TRPM7 protein, human