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 (109)Cd uptake and cytotoxicity in MC3T3-E1 osteoblasts. Time-dependent accumulation of (109)Cd 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 (109)Cd uptake suggesting the involvement of non-selective cationic channels. The Mg-sensitive part of (109)Cd uptake increased at acidic pH, a condition known to stimulate TRPM7 channel activity. Stimulating TRPM7 channel activity by cellular Mg starvation enhanced (109)Cd 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.