Involvement of transient receptor potential melastatin-related 7 (TRPM7) channels in cadmium uptake and cytotoxicity in MC3T3-E1 osteoblasts

Exposure to cadmium (Cd) disrupts bone metabolism, causing osteoporosis. Impaired vitamin D metabolism was initially proposed as the underlying mechanism, yet recent studies argue for the direct effect of Cd on bone cells. This study aimed at characterizing 109Cd uptake and cytotoxicity in MC3T3-E1 osteoblasts. Time-dependent accumulation of 109Cd was observed with a 50% lethal concentration (LC 50) of 9.6 ± 1.2 μM at 24-h. Reducing extracellular calcium (Ca) or magnesium (Mg) increased Cd cytotoxicity. The presence of Ca, Mg, zinc or gadolinium decreased 109Cd uptake suggesting the involvement of non-selective cationic channels. The Mg-sensitive part of 109Cd uptake increased at acidic pH, a condition known to stimulate TRPM7 channel activity. Stimulating TRPM7 channel activity by cellular Mg starvation enhanced 109Cd uptake. Silencing TRPM7 channel expression abolished the Mg-sensitive and the Mg starvation-induced uptake indicating that TRPM7 is involved in Cd transport in osteoblasts.