Abstract
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.
Highlights
Cadmium, a heavy metal and persistent environmental toxicant, has a biological half-life of 10–30 years [1,2]
Primary bone marrow mesenchymal stem cells (BMMSCs) were isolated from rat bone marrow and passaged
Confirming the identity of BMMSCs, flow cytometry analysis showed that the cells had high levels of CD44 (99.80 ± 0.19%) and CD90 (96.54 ± 0.46%) but limited expression of the hematopoietic marker CD45 (1.93 ± 0.56%) (Figure 1B)
Summary
A heavy metal and persistent environmental toxicant, has a biological half-life of 10–30 years [1,2]. It is released into the environment through natural processes and human activities, such as mining and smelting, which may lead to contamination of soils and to increased cadmium uptake by crops and vegetables that are grown for human consumption [3]. Exposure to high levels to cadmium reduces bone mineral density (BMD) manifested as osteoporosis and osteomalacia [4]. Population-based studies from several countries reveal an association between decreased BMD and low-level environmental exposure to Cd [3]. The molecular and genetic basis by which CdCl2 causes diseases, remains largely unknown
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