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Open AccessArticle

Wnt/β-Catenin Pathway Is Involved in Cadmium-Induced Inhibition of Osteoblast Differentiation of Bone Marrow Mesenchymal Stem Cells

by Lu Wu 1,2,†, Qinzhi Wei 3,†, Yingjian Lv 4,†, Junchao Xue 1,2, Bo Zhang 3, Qian Sun 1,2, Tian Xiao 1,2, Rui Huang 4, Ping Wang 4, Xiangyu Dai 1,2, Haibo Xia 1,2, Junjie Li 1,2, Xingfen Yang 3,* and Qizhan Liu 1,2,*
1
Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China
2
The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
3
Food Safety and Health Research Center, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China
4
Guangdong Provincial Center for Disease Control and Prevention, Guangzhou 511430, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(6), 1519; https://doi.org/10.3390/ijms20061519
Received: 20 February 2019 / Revised: 18 March 2019 / Accepted: 22 March 2019 / Published: 26 March 2019
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. View Full-Text
Keywords: osteogenesis; bone marrow mesenchymal stem cells; cadmium; Wnt/β-catenin pathway osteogenesis; bone marrow mesenchymal stem cells; cadmium; Wnt/β-catenin pathway
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MDPI and ACS Style

Wu, L.; Wei, Q.; Lv, Y.; Xue, J.; Zhang, B.; Sun, Q.; Xiao, T.; Huang, R.; Wang, P.; Dai, X.; Xia, H.; Li, J.; Yang, X.; Liu, Q. Wnt/β-Catenin Pathway Is Involved in Cadmium-Induced Inhibition of Osteoblast Differentiation of Bone Marrow Mesenchymal Stem Cells. Int. J. Mol. Sci. 2019, 20, 1519.

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