Crosstalk between Wnt/β-catenin signaling and NF-κB signaling contributes to apical periodontitis

In physiology conditions, the crosstalk of signaling pathways has been considered to extend the functions of individual pathways and results in a more complex regulatory network. The Wnt3a/β-catenin and NF-κB signaling pathways have been demonstrated involving in apical periodontitis (AP). As AP progresses, ultimately causes tooth loss. In the present study, we investigate the contribution of the crosstalk between the Wnt3a/β-catenin and NF-κB signaling pathways to the development of AP. Clinically, utilizing 60 human AP and healthy tissues (30 samples for each group), we found that the expression levels of Wnt3a/β-catenin and NF-κB were elevated in the Ap tissues compared to that in the healthy group. To further study the roles of Wnt3a/β-catenin and NF-κB signaling pathways in the development of AP, and the contribution of the crosstalk between these two signaling pathways to AP, we established the AP animal model and observed that, first, both pathways are activated in the AP group compared to the control group. Interestingly, by immunoprecipitation and western blot experiments, we revealed that there is greater interaction between NF-κB (phorspho-p65) and β-catenin in AP tissues compared to the control tissues. Importantly, when the NF-κB signaling pathway was blocked by its inhibitor, pyrrolidine dithiocarbamate (PDTC), the activity of the Wnt3a/β-catenin signaling pathway was abolished, and consequently led to the attenuation of the inflammation response in LPS-induced human periodontal ligament cells (hPDLCs). Thus, our data indicate that the crosstalk between Wnt3a/β-catenin and NF-κB signaling pathway contributes to the development of AP, and provide a therapeutic strategy for the treatment of AP as well.