Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
Food Chem Toxicol. 2013 Oct;60:530-5. doi: 10.1016/j.fct.2013.08.017. Epub 2013 Aug 15.
Low level of cadmium (Cd) exposure may enhance osteoclasts formation in vitro. The aim of the study was to observe the effects of Cd on osteoclasts formation in vivo. Sprague-Dawley male rats were divided into 4 groups which were given Cd via drinking water at concentrations of 0, 2, 10 and 50 mg/L for 12 weeks. At the 12th week, urine samples were collected from all of the rats. All rats were then sacrificed and the blood was collected for biomarkers assay. Bone tissues were dissected for mineral density determinations, histological investigation, tartrate resistant acid phosphatase staining and immunohistochemical staining. The bone mineral density and bone microstructure index of rats treated with 50mg Cd/L were obviously lower than in control rats. Histochemical investigation showed that Cd could induce osteoclasts formation in a dose-dependent manner. Tartrate resistant acid phosphatase 5b levels in rats treated with Cd were higher than the control. Immunohistochemical investigation showed that Cd could enhance receptor-activated nuclear factor kappa B ligand expression (RANKL) and inhibit osteoprotegerin (OPG) expression. Our study evidences in vivo that excessive bone resorption mediated via osteoclasts is an important way for Cd toxic effects on bone and OPG/RANKL may play an important role.
低水平的镉(Cd)暴露可能会增强体外破骨细胞的形成。本研究旨在观察 Cd 对体内破骨细胞形成的影响。雄性 Sprague-Dawley 大鼠分为 4 组,通过饮用水给予浓度为 0、2、10 和 50mg/L 的 Cd,为期 12 周。在第 12 周,收集所有大鼠的尿液样本。所有大鼠均被处死并采集血液用于生物标志物检测。分离骨组织进行矿物质密度测定、组织学研究、抗酒石酸酸性磷酸酶染色和免疫组织化学染色。用 50mg Cd/L 处理的大鼠的骨矿物质密度和骨微结构指数明显低于对照组。组织化学研究表明,Cd 可以以剂量依赖的方式诱导破骨细胞形成。Cd 处理大鼠的抗酒石酸酸性磷酸酶 5b 水平高于对照组。免疫组织化学研究表明,Cd 可以增强核因子 kappa B 受体激活配体(RANKL)的表达,抑制骨保护素(OPG)的表达。本研究在体内证实,破骨细胞介导的过度骨吸收是 Cd 对骨骼毒性作用的重要途径,而 OPG/RANKL 可能发挥重要作用。