Laboratoire du Métabolisme osseux, Centre de recherche BioMed, Département des Sciences Biologiques, Université du Québec à Montréal, Montreal, Quebec, Canada.
Toxicol Lett. 2010 Dec 15;199(3):357-63. doi: 10.1016/j.toxlet.2010.09.019. Epub 2010 Oct 13.
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.
镉（Cd）暴露会破坏骨骼代谢，导致骨质疏松症。最初提出维生素 D 代谢受损是其潜在机制，但最近的研究认为 Cd 对骨细胞有直接影响。本研究旨在研究（109）Cd 在 MC3T3-E1 成骨细胞中的摄取和细胞毒性。结果发现，（109）Cd 的摄取呈时间依赖性，24 小时时 50%的半数致死浓度（LC50）为 9.6±1.2μM。减少细胞外钙（Ca）或镁（Mg）可增加 Cd 的细胞毒性。Ca、Mg、锌或钆的存在减少了（109）Cd 的摄取，表明非选择性阳离子通道的参与。在酸性 pH 条件下，（109）Cd 摄取的 Mg 敏感部分增加，已知这种条件可刺激 TRPM7 通道活性。通过细胞内 Mg 饥饿刺激 TRPM7 通道活性增强了（109）Cd 的摄取。沉默 TRPM7 通道表达可消除 Mg 敏感和 Mg 饥饿诱导的摄取，表明 TRPM7 参与了成骨细胞中的 Cd 转运。
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