Protective roles of FICZ and aryl hydrocarbon receptor axis on alveolar bone loss and inflammation in experimental periodontitis

Abstract

Aim: The aryl hydrocarbon receptor (AhR)-ligand axis has been shown to be involved in inflammatory diseases and bone homeostasis. However, the activation of AhR signalling pathway and the possible functions of AhR ligands in periodontitis are underexplored. This study investigated the expression of the AhR target gene cytochrome P450 subfamily B member 1 (CYP1B1) and the functions and mechanisms of the AhR ligand 6 formylindolo[3,2-b]carbazole (FICZ) in periodontitis. Materials and Methods: CYP1B1 expression was detected in human periodontitis samples, mice with ligature-induced periodontitis and lipopolysaccharide (LPS)-induced inflammation in periodontal ligament cells (PDLCs) in vitro. FICZ was administered topically or systemically. The therapeutic functions of FICZ were detected via qPCR, micro-computed tomography and immunohistochemistry. Finally, the mechanisms of AhR signalling in periodontitis were investigated by cell assays. Results: CYP1B1 expression was downregulated in periodontitis. FICZ rescued the alveolar bone loss and mitigated the inflammatory cytokines in periodontitis mice. In vitro, FICZ pre-treatment reduced the LPS-induced inflammation in PDLCs via the increased phosphorylation of STAT3. Additionally, FICZ prompted the mineralization of PDLCs via activation of the Wnt/β-catenin signalling pathway. Conclusion: AhR signalling pathway is suppressed in periodontitis and the AhR ligand FICZ can prevent periodontitis. K E Y W O R D S AhR signalling, CYP1B1, FICZ, inflammation, periodontitis | 883 HUANG et Al.

Periodontal Inflammation and Systemic Diseases: An Overview

“…Interestingly, a number of clinical studies in humans have shown that excessive production of IL-17 is associated with periodontitis. Similar protective roles have been shown in the case of FICZ (tryptophan photooxidation product 6-formylindolo[3,2b]carbazole, a physiological ligand for the mammalian aryl hydrocarbon receptor to which it binds inducing expression of cytochrome P450) and molecules in the aryl hydrocarbon receptor axis in relation to alveolar bone loss and inflammation in experimental (murine) periodontitis (Huang et al, 2019).…”

“…EGFR (epidermal growth factor receptor) signaling has been found to downregulate the αvβ6 integrin, thus promoting periodontal inflammation and bone loss (Bi et al, 2020 ). The protective effects of 6-Formylindolo[3,2-b]carbazole (FICZ) and the aryl hydrocarbon receptor signaling pathway on alveolar bone loss and inflammation have been recently discussed in the context of experimental periodontitis (Huang et al, 2019 ).…”

Chitosan hydrogel incorporated with dental pulp stem cell-derived exosomes alleviates periodontitis in mice via a macrophage-dependent mechanism

“…LEGENDplex™ bead-based immunoassays and PCR analysis showed that the levels of various inflammatory mediators were decreased in DPSC-Exo/CS-treated P mice compared with those of CS-treated P mice. Previous studies indicated that the activation of NF-κB and p38 MAPK signalling is responsible for persistent inflammation of the periodontium [ 40 , 46 ]. Our study showed that DPSC-Exo/CS infusion downregulated the activation of NF-κB and p38 MAPK signalling in the periodontium of P mice.…”

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

“…In vitro experiments revealed that FICZ pre-treatment reduced LPS-induced inflammation in periodontal ligament cells via increased phosphorylation of STAT3. FICZ also promoted the mineralization of periodontal ligament cells (PDLCs) via activation of the Wnt/β-catenin signaling pathway [59].…”