Arsenic may be involved in fluoride-induced bone toxicity through PTH/PKA/AP1 signaling pathway

• PTH/PKA/AP1 pathway may play an important role in bone damage of fluorine.
• It was first found that arsenic may indirectly influence bone damage of fluorine.
• It has the important theoretical significance and practical value for the study of mechanism on syndrome of endemic arsenism and fluorosis.

Chronic exposure to combined fluoride and arsenic continues to be a major public health problem worldwide, affecting thousands of people. In recent years, more and more researchers began to focus on the interaction between the fluorine and the arsenic. In this study, the selected investigation site was located in China. The study group was selected from people living in fluoride–arsenic polluted areas due to burning coal. The total number of participants was 196; including the fluoride–arsenic anomaly group (130) and the fluoride–arsenic normal group (63). By observing the changes in gene and protein expression of PTH/PKA/AP1 signaling pathway, the results show that fluoride can increase the expression levels of PTH, PKA, and AP1, but arsenic can only affect the expression of AP1; fluoride and arsenic have an interaction on the expression of AP1. Further study found that fluoride and arsenic can affect the mRNA expression level of c-fos gene (AP1 family members), and have an interaction on the expression of c-fos, but not c-jun. The results indicate that PTH/PKA/AP1 signaling pathway may play an important role in bone toxicity of fluoride. Arsenic can affect the expression of c-fos, thereby affecting the expression of transcription factor AP1, indirectly involved in fluoride-induced bone toxicity.

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