Cadmium is a common environmental pollutant that causes bone damage. However, the effects of cadmium on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) and its mechanism of action in this process are unclear. Here, we determined the effects of cadmium chloride (CdCl2) on the osteogenic differentiation of BMMSCs and the potential mechanism involved in this process. As determined in the present investigation, CdCl2, in a concentration-dependent manner, affected the viability of BMMSCs and their cytoskeletons. Exposure to 0.1 or 0.2 µM CdCl2 inhibited osteogenic differentiation of BMMSCs, which was reflected in the down-regulation of osteoblast-related genes (ALP, OCN, Runx2, OSX, and OPN); in suppression of the protein expression of alkaline phosphatase (ALP) and runt-related transcription factor 2 (Runx2); and in decreased ALP activity and capacity for mineralization. Moreover, mRNA microarray was performed to determine the roles of these factors in BMMSCs treated with CdCl2 in comparison to control BMMSCs. As determined with the microarrays, the Wingless-type (Wnt), mothers against decapentaplegic and the C. elegans gene Sam (SMAD), and Janus kinase-Signal Transducers and Activators of Transcription (JAK-STAT) signaling pathways were involved in the effects caused by CdCl2. Moreover, during differentiation, the protein levels of Wnt3a, β-catenin, lymphoid enhancer factor 1 (LEF1), and T-cell factor 1 (TCF1) were reduced by CdCl2. The current research shows that CdCl2 suppresses the osteogenesis of BMMSCs via inhibiting the Wnt/β-catenin pathway. The results establish a previously unknown mechanism for bone injury induced by CdCl2.

This study aimed to assess the association between osteoporosis and long-term environmental Cd exposure through diet in southern China. A total of 1116 subjects from a Cd-polluted area and a non-Cd-polluted area were investigated. All subjects met the criteria of having been living in the investigated area for more than 15 years and lived on a subsistence diet of rice and vegetables grown in that area. Besides bone mineral density, the levels of urinary markers of early renal impairment, such as urinary N-acetyl-β-D-glucosaminidase (NAG), α -microglobulin, β -microglobulin, and urinary albumin, were also determined. Urinary Cd concentrations of all studied subjects ranged from 0.21 to 87.31 µg/g creatinine, with a median of 3.97 µg/g creatinine. Multivariate linear regression models indicated a significant negative association of urinary Cd concentrations with bone mineral density. In logistic regression models, both categorical and continuous urinary Cd concentrations were positively associated with osteoporosis. Subjects in the second, third, and fourth quartiles of urinary Cd concentration had greater odds of osteoporosis compared with subjects in the first quartile (odds ratio [OR] = 3.07, 95% confidence interval [CI], 1.77 to 5.33; OR = 4.63, 95% CI, 2.68 to 7.98; OR = 9.15, 95% CI, 5.26 to 15.94, respectively). Additional adjustment for levels of urinary markers did not attenuate the associations. No evidence existed of an interaction between urinary Cd concentration and renal function using levels of urinary markers, and estimated glomerular filtration rate (eGFR). In all subjects, the benchmark dose and benchmark dose lower bound were 1.14 (0.61) and 2.73 (1.83) µg/g creatinine, with benchmark response set at 5% and 10%, respectively. The benchmark dose of urinary Cd was lower in women than in men. This study demonstrated an inverse association between the body burden of Cd and osteoporosis. The toxic effect of Cd on bone may occur in parallel to nephrotoxicity. © 2017 American Society for Bone and Mineral Research.

The present study was designed to evaluate the effects of Prunella Vulgaris (P. vulgaris) on the immune function in mice. The mice were randomly divided into one control group and three treatment groups of 10 mice each. The control group received pure water and the treatment groups received P. vulgaris extract at concentrations of 0.15, 0.30 and 0.90 g/kg BW orally for 30 days, respectively. Changes in cell immune function, non-specific immunity and humoral immunity function were evaluated. Active lymphocytes and T lymphocyte subsets were determined by fluorescence-activated cell sorting (FACS). Certain Serum concentrations of cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that, for cell immune function, compared with the control group, foot pad thickness in high dose group increased significantly (p<0.01), whereas no significant difference in the proliferative ability of splenic lymphocytes was observed among all groups (p>0.05). For non-specific immunity, NK cell activity increased significantly in a dose-dependent manner in P. vulgaris treated mice (p<0.01), mononuclear-macrophage function in medium and high dose P. vulgaris treated mice were significantly higher than that of the control group (p<0.05). For humoral immunity, no significant differences were observed in terms of the half value of hemolysis (HC50), number of hemolytic plaques and serum IgG level (p>0.05). The percentage of active T and Th lymphocytes of mice peripheral blood in high dose group were significantly higher than that of the control group (p<0.01). There was no significant difference in serum levels of IL-1β, IL-4, IL-10 and IFN-γ among all of the four groups (p>0.05). The data indicated that 0.90 g/kg BW P. vulgaris extract (equivalent to 7.5 g/kg BW crude drug) had some effect on cellular immune function and non-specific immune function in mice.

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