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.

中文翻译：

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镉对雌性小鼠骨损伤破骨细胞分化的影响

镉 (Cd) 是一种有毒重金属，是一种职业危害和环境污染物有毒重金属，在体内积累后会导致骨质疏松症。本研究的目的是研究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，给予不同浓度 Cd（0、5 和 25 mg/L）的饮用水，持续 16 周，收集尿液和血液后处死小鼠。测定Cd、钙（Ca）、磷（P）、微量元素及部分生化指标水平，将骨固定于4%甲醛溶液中进行组织学观察。分离骨髓细胞以确定破骨细胞相关 mRNA 和蛋白质的表达。血液、尿液中的 Cd 增加，和骨骼以剂量依赖性方式响应饮用水中的 Cd。与对照组相比，骨中铁（Fe）、锰（Mn）和锌（Zn）的含量显着增加，而钙和磷的含量降低。Cd影响骨骼的组织结构，分别诱导血清中抗酒石酸酸性磷酸酶5b（TRACP-5b）和雌二醇的上调和下调。Cd对血清中碱性磷酸酶活性没有显着影响。破骨细胞标记蛋白，包括 TRACP、组织蛋白酶 K、基质金属蛋白 9 和碳酸酐酶在 Cd 处理的骨髓细胞中的表达均增加。Cd显着增加核因子κB配体（RANKL）受体激活剂的表达，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 暴露破坏了骨微结构，促进了骨组织中破骨细胞的形成，加速了骨吸收，其中 OPG/RANKL 通路可能起重要作用。