Effect of Cadmium Exposure on Osteoporosis: Activating the P2X7R-Mediated Classical Pyroptosis Pathway Induced Osteoblast Death

Cadmium, a global environmental pollutant, can accumulate in the bone tissue, representing a major risk factor for osteoporosis. However, the specific mechanisms remain unclear. First, a 4 month cadmium exposure study via drinking water was used to investigate its bone toxicity effects. Cadmium exposure significantly reduced bone density. Subsequently, we established osteoblast model cadmium exposure concentration points. Cadmium exposure induced osteoblast pyroptosis from the perspectives of morphology and the molecular level. The underlying mechanisms involve a P2X7R-medicated pyroptosis pathway. Finally, a <i>p2x7r^-/-</i> mouse fed cadmium-exposed water for 4 months and <i>p2x7r^-/-</i>osteoblasts exposed to cadmium, were used to validate the effect of core target P2X7R. The results demonstrated that <i>p2x7r</i> gene deletion obviously reduced pyroptosis-like osteoblasts, and <i>p2x7r</i> knockout mice did not develop osteoporosis; the expression of pyroptosis proteins was not significantly increased. Our study provides new insights into the damage caused by environmental pollutants to the body.