Cadmium exposure triggers osteoporosis in duck via P2X7/PI3K/AKT-mediated osteoblast and osteoclast differentiation

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. [Display omitted] •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.