College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
Environ Toxicol. 2020 Apr;35(4):487-494. doi: 10.1002/tox.22884. Epub 2019 Dec 3.
Cadmium (Cd) is a toxic heavy metal that represents an occupational hazard and environmental pollutant toxic heavy metal, which can cause osteoporosis following accumulation in the body. The purpose of this study was to investigate the effect of Cd on bone tissue osteoclast differentiation in vivo. Female BALB/c mice were randomly divided into three groups and given drinking water with various concentrations of Cd (0, 5, and 25 mg/L) for 16 weeks, after which the mice were sacrificed after collecting urine and blood. The level of Cd, calcium (Ca), phosphorus (P), trace elements, and some biochemical indicators were measured, and the bone was fixed in a 4% formaldehyde solution for histological observation. Bone marrow cells were isolated to determine the expression of osteoclast-associated mRNA and proteins. Cd was increased in the blood, urine, and bone in response to Cd in drinking water in a dose-dependent manner. The content of iron (Fe), manganese (Mn), and zinc (Zn) was significantly increased, whereas Ca and P were decreased in bone compared to the control group. Cd affected the histological structure of the bone, and induced the upregulation and downregulation of tartrate-resistant acid phosphatase 5b (TRACP-5b) and estradiol in the serum, respectively. Cd had no significant effect on the alkaline phosphatase activity in the serum. The expression of osteoclast marker proteins, including TRACP, cathepsin K, matrix metalloprotein 9, and carbonic anhydrases were all increased in the Cd-treated bone marrow cells. Cd significantly increased the expression of receptor activator of nuclear factor kappa B ligand (RANKL), but had lower effect on the expression of osteoprotegerin (OPG) in both bone marrow cells and bone tissue. Thus, Cd exposure destroyed the bone microstructure, promoted the formation of osteoclasts in the bone tissue, and accelerated bone resorption, in which the OPG/RANKL pathway may play an important role.
镉 (Cd) 是一种有毒重金属，是职业危害和环境污染物有毒重金属，它在体内积累后可导致骨质疏松症。本研究旨在探讨镉对体内骨组织破骨细胞分化的影响。将雌性 BALB/c 小鼠随机分为三组，分别给予含不同浓度 Cd（0、5 和 25mg/L）的饮用水 16 周，然后收集尿液和血液处死小鼠。测定 Cd、钙（Ca）、磷（P）、微量元素和部分生化指标，4%甲醛溶液固定骨骼进行组织学观察。分离骨髓细胞，测定破骨细胞相关 mRNA 和蛋白的表达。随着饮用水中 Cd 剂量的增加，血液、尿液和骨骼中的 Cd 呈剂量依赖性增加。与对照组相比，骨骼中的铁（Fe）、锰（Mn）和锌（Zn）含量明显增加，而 Ca 和 P 含量降低。Cd 影响骨骼的组织学结构，分别上调和下调血清中抗酒石酸酸性磷酸酶 5b（TRACP-5b）和雌二醇的表达。Cd 对血清碱性磷酸酶活性无明显影响。Cd 处理的骨髓细胞中破骨细胞标志物蛋白，包括 TRACP、组织蛋白酶 K、基质金属蛋白酶 9 和碳酸酐酶的表达均增加。Cd 显著增加了核因子 κB 受体激活剂配体（RANKL）的表达，但对骨髓细胞和骨组织中骨保护素（OPG）的表达影响较小。因此，Cd 暴露破坏了骨的微观结构，促进了骨组织中破骨细胞的形成，加速了骨吸收，其中 OPG/RANKL 途径可能发挥重要作用。
