Environmental level of cadmium exposure stimulates osteoclasts formation in male rats

• Environmental level of cadmium exposure induced obvious bone damage.
• Osteoclasts formation was induced by environmental level of cadmium exposure.
• OPG/RANKL pathway may involve in osteoclast formation induced by cadmium.

Low level of cadmium (Cd) exposure may enhance osteoclasts formation in vitro. The aim of the study was to observe the effects of Cd on osteoclasts formation in vivo. Sprague-Dawley male rats were divided into 4 groups which were given Cd via drinking water at concentrations of 0, 2, 10 and 50 mg/L for 12 weeks. At the 12th week, urine samples were collected from all of the rats. All rats were then sacrificed and the blood was collected for biomarkers assay. Bone tissues were dissected for mineral density determinations, histological investigation, tartrate resistant acid phosphatase staining and immunohistochemical staining. The bone mineral density and bone microstructure index of rats treated with 50 mg Cd/L were obviously lower than in control rats. Histochemical investigation showed that Cd could induce osteoclasts formation in a dose-dependent manner. Tartrate resistant acid phosphatase 5b levels in rats treated with Cd were higher than the control. Immunohistochemical investigation showed that Cd could enhance receptor-activated nuclear factor kappa B ligand expression (RANKL) and inhibit osteoprotegerin (OPG) expression. Our study evidences in vivo that excessive bone resorption mediated via osteoclasts is an important way for Cd toxic effects on bone and OPG/RANKL may play an important role.