Mesenchymal stem cells (MSCs) have the potential to differentiate into several cell types and provide an attractive source of autologous cells for regenerative medicine. However, their cellular biology is not fully understood. Similar to Ca2+, extracellular Mg2+ plays an important role in the functions of the skeletal system. Here, we examined the effects of extracellular Mg2+ on the deposition of calcium phosphate matrix and Ca2+ signaling with or without ATP stimulation in human bone marrow-derived mesenchymal stem cells (hBMSCs). We found that high extracellular Me concentration ([Mg2+](e)) inhibited extracellular matrix mineralization in hBMSCs in vitro. hBMSCs also produced a dose-dependent decrease in the frequency of calcium oscillations during [Mg2+](e) elevation with a slight suppression on oscillation amplitude. In addition, spontaneous ATP release was inhibited under high [Mg2+](e) levels and exogenous ATP addition stimulated oscillation reappear. Taken together, our results indicate that high [Mg2+](e) modulates calcium oscillations via suppression of spontaneous ATP release and inactivates purinergic receptors, resulting in decreased extracellular mineralized matrix deposition in hBMSCs. Therefore, the high magnesium environment created by the rapid corrosion of Mg alloys may result in the dysfunction of calcium-dependent physiology processes and be disadvantageous to hBMSCs physiology. (C) 2014 Elsevier Inc. All rights reserved.