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Effects of Co-exposure to Fluoride and Arsenic on TRAF-6 Signaling and NF-κB Pathway of Bone Metabolism

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Abstract

Little is known about the combined effect of fluoride (F) and arsenic (As) on bone metabolism. This study aims to explore the effect of co-exposure to F and As on the expressions of TNF receptor-associated factor 6 (TRAF-6), nuclear factor-kappa B (NF-κB), and the related factors in cell and animal experiments. With the rats exposed to different doses of F, As, and combined F-As, we found that F exposure doses were positively correlated with the protein expression of receptor activator of nuclear factor-kappa B ligand (RANKL), receptor activator of nuclear factor-kappa B (RANK), TRAF-6, NF-κB, and nuclear factor of activated T cells (NFAT-c1) (P < 0.001). As exposure doses were negatively correlated with RANK, TRAF-6, NF-κB, and NFAT-c1 (P < 0.001). The effect of F and As interaction on the protein expression of RANKL, TRAF-6, NF-κB, and NFAT-c1 was significant in bone tissue (P < 0.05). In the cellular experiment, F could promote the mRNA expression of RANK, TRAF-6, and NFAT-c1. A higher concentration of As could inhibit the mRNA expression of Tartrate-resistant acid phosphatase (TRAP), RANK, TRAF-6, and NFAT-c1. The effect of F and As interaction on the mRNA expression of TRAP, RANK, TRAF-6, and NFATc1 in osteoclasts was significant (P < 0.001). In conclusion, the expression of TRAF-6 and NF-κB pathway was affected by F and As co-exposure in osteogenic differentiation, and As could antagonize the promoting effect of F on the expression of TRAF-6, TRAP, RANKL, RANK, NF-κB, and NFAT-c1 in these exposure levels. These results could provide a scientific basis for understanding the interaction of F and As in bone formation.

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Data Availability

Data are available from the corresponding author upon reasonable request.

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Funding

This study was supported by the National Natural Science Foundation of China (No. 82173566).

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Authors and Affiliations

  1. School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 550025, China

    Chan Nie, Junwei Hu, Bingjie Wang, Hao Li, Xing Yang & Feng Hong

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Contributions

Chan Nie analyzed the data, prepared figures and tables, and wrote the paper. Bingjie Wang, Hao Li, and Xing Yang designed and performed the experiments, and prepared figures and tables. Feng Hong conceived the experiments and reviewed and edited the manuscript. All authors read and approved the manuscript.

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Correspondence to Feng Hong.

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This study was performed according to the national and institutional guidelines and approved by the Animal Experimental Ethical Committee of Guizhou Medical University (approval number: 1413060).

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Nie, C., Hu, J., Wang, B. et al. Effects of Co-exposure to Fluoride and Arsenic on TRAF-6 Signaling and NF-κB Pathway of Bone Metabolism. Biol Trace Elem Res 201, 4447–4455 (2023). https://doi.org/10.1007/s12011-022-03508-9

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