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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\u2009mg\/L) for 16\u2009weeks, 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\u2010associated mRNA and proteins. Cd was increased in the blood, urine, and bone in response to Cd in drinking water in a dose\u2010dependent 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\u2010resistant acid phosphatase 5b (TRACP\u20105b) 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\u2010treated 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.<\/jats:p>","DOI":"10.1002\/tox.22884","type":"journal-article","created":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T12:27:49Z","timestamp":1575376069000},"page":"487-494","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Effect of cadmium on osteoclast differentiation during bone injury in female mice"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8755-8231","authenticated-orcid":false,"given":"Shuangjiang","family":"He","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine Yangzhou University  Yangzhou China"},{"name":"Jiangsu Co\u2010innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses  Yangzhou 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