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

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. Highlights • TRPM7/MagT1 co-silencing inhibits cell growth and activates autophagy in human mesenchymal stem cells. • TRPM7/MagT1 co-silencing induces the expression of RUNX2 and OSTERIX while COL1A1 is upregulated as much as in the controls. • TRPM7/MagT1 co-silencing, however, does not impact on the acquisition of a full osteogenic phenotype. [ABSTRACT FROM AUTHOR]