Cadmium induces bone loss and inhibits bone formation in male mice / 中国职业医学

ABSTRACT

OBJECTIVE: To explore the effect of cadmium on bone formation and its mechanism in male mice. METHODS: i) The specific pathogen-free C57 BL/6 J wild-type male mice were divided into control group and cadmium exposure group, with 10 mice in each group. Mice in the cadmium exposure group were intraperitoneally injected with 2 mg/kg body weight cadmium chloride twice a week for eight weeks, and mice in the control group were intraperitoneally injected with the same amount of 0.9% sodium chloride solution. After that, the bone mineral density and bone microstructure of the femur of mice were detected by a high-resolution microcomputed tomography scanner. ii) Human SV40-transfected osteoblast cells(hFOB1.19) were divided into control group and cadmium exposure group. The cadmium exposure group was treated with 0.5 μmol/L cadmium chloride solution, cells in the control group were given an equal volume of α-low-limit minimal medium. After culture, the differentiation and mineralization ability of hFOB1.19 cells were analyzed by alkaline phosphatase(ALP) and alizarin red staining, respectively. Cell viability was examined by CCK-8 assay. The protein expression of Janus kinase 2(JAK2), total signal of transducers and activator of transcription 3(tSTAT3) and phosphorylated signal transducers and activator of transcription 3(pSTAT3) was detected by Western blotting. The expression of osteoblastic marker genes ALP, Runt-related transcription factor 2(RUNX2) and osteocalcin(OCN) was detected by real-time quantitative polymerase chain reaction.RESULTS: Compared with the control group, the average bone mineral density decreased(P<0.01), bone volume fraction decreased(P<0.05), the bone trabecula thickness became thinner(P<0.01), the number of bone trabecula decreased(P<0.05), trabecular bone spacing increased(P<0.05) in the femur of mice in cadmium exposure group. The viability of hFOB1.19 cells was decreased [(100.0±10.8)% vs(49.1±8.2)%, P<0.01]. The differentiation ability of osteoblasts was reduced and the mineralization was inhibited. The relative expression levels of JAK2 and pSTAT3 in cells decreased(all P<0.05) and the relative expression levels of osteoblast marker genes ALP, RUNX2 and OCN decreased(all P<0.01).CONCLUSION: Cadmium can induce mice bone loss, which may be due to its inhibition of osteoblastic function by reducing the expression of JAK2 and STAT3 proteins.