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Cadmium is a common environmental pollutant that accumulates in the bone and kidneys and causes severe health and social problems. However, the effects of Cd on the occurrence of osteoporosis and its mechanism of action in this process are unclear. To test whether Cd-induced osteoporosis is mediated via P2X7/PI3K/AKT signaling, duck bone marrow mesenchymal stem cells (BMSCs) and bone marrow macrophage cells (BMMs) were treated with Cd for 5 days, and duck embryos were treated with Cd. Micro-CT analysis indicated that Cd-induced osteoporosis occurs in vivo , and histopathology and immunohistochemical analyses also revealed that Cd induced bone damage and the downregulation of osteogenic and bone resorption-related proteins. Cd exposure significantly inhibited the differentiation of BMSCs and BMMs into osteoblasts and osteoclasts in vitro , and promoted osteoblast and osteoclast apoptosis. Cd exposure significantly downregulated the P2X7/PI3K/AKT signaling pathway in vivo and in vitro , and inhibition of this signaling pathway significantly aggravated osteoblast and osteoclast differentiation. Cd exposure also upregulated the OPG/RANKL ratio in vivo and in vitro , further inhibiting osteoclast differentiation. These results demonstrate that Cd causes osteoporosis in duck by inhibiting P2X7/PI3K/AKT signaling and increasing the OPG/RANKL ratio. These results establish a previously unknown mechanism of Cd-induced osteoporosis. Cadmium is a widespread environmental pollutant that accumulates in bone and causes bone damage. Our findings demonstrate that Cd exposure inhibits osteoblast and osteoclast differentiation, and induces apoptosis, finally resulting in osteoporosis. P2X7/PI3K/AKT and OPG/RANKL signaling play an essential role in Cd-induced osteoporosis. Unlabelled Image • Cadmium (Cd) exposure causes osteoporosis in ducks. • Cd induced osteoporosis is related to defects in osteogenic differentiation. • Cd exposure decreases protein levels of key osteogenic and bone resorption-related proteins. • Cd inhibtes the differentiation of osteoclast and osteoblase by inhibiting P2X7/PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a widespread environmental contaminant that causes severe bone metabolism disease, such as osteoporosis, osteoarthritis, and osteomalacia. The present review aimed to explore the molecular mechanisms of Cd-induced bone injury starting from bone cell function and teeth development. Cd inhibits the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts, and directly causes BMSC apoptosis. In the case of osteoporosis, Cd mainly affects the activation of osteoclasts and promotes bone resorption. Cd-induces osteoblast injury and oxidative stress, which causes DNA damage, mitochondrial dysfunction, and endoplasmic reticulum stress, resulting in apoptosis. In addition, the development of osteoarthritis (OA) might be related to Cd-induced chondrocyte damage. The high expression of metallothionein (MT) might reduce Cd toxicity toward osteocytes. The toxicity of Cd toward teeth mainly focuses on enamel development and dental caries. Understanding the effect of Cd on bone cell function and teeth development could contribute to revealing the mechanisms of Cd-induced bone damage. This review explores Cd-induced bone disease from cellular and molecular levels, and provides new directions for removing this heavy metal from the environment. Cd exposure causes severe bone metabolism disease. Apoptosis and differentiation play an essential role in Cd-induced osteoporosis. The development of osteoarthritis (OA) might be related to Cd-induced chondrocyte damage. The expression of MT may affect Cd-induced osteocytes damage. The toxicity of Cd toward teeth is mainly focused on enamel development and dental caries. Therefore, bone cells function and teeth development is mainly present manner of Cd toxicity. Unlabelled Image • Cd causes severe bone metabolism disease. • Cd-induces bone injury via affecting bone cell formation and function. • Apoptosis is main death manner by Cd-induced bone cell. • The toxicity of Cd toward teeth is mainly affected enamel development and dental caries. [ABSTRACT FROM AUTHOR]