TRPM7 and MagT1 regulate the proliferation of osteoblast-like SaOS-2 cells through different mechanisms

A correct magnesium (Mg²⁺) intake is essential for bone health. In particular, Mg²⁺ deficiency inhibits the proliferation of osteoblast-like SaOS-2 cells by increasing nitric oxide (NO) production through the upregulation of inducible NO synthase. At the moment, little is known about the expression and the role of TRPM7, a channel/enzyme involved in Mg²⁺ uptake, and MagT1, a Mg²⁺ selective transporter, in SaOS-2 cells. Here, we demonstrate that TRPM7 is not modulated by different extracellular concentrations of Mg²⁺ and its silencing exacerbates growth inhibition exerted by low Mg²⁺ through the activation of inducible NO synthase and consequent accumulation of NO. Moreover, MagT1 is upregulated in SaOS-2 cultured in high Mg²⁺ and its silencing inhibits the growth of SaOS-2 cultured in media containing physiological or high Mg²⁺, without any modulation of NO production. We propose that TRPM7 and MagT1 are both involved in regulating SaOS-2 proliferation through different mechanisms.