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.
BackgroundSenescence-related impairment of proliferation and differentiation limits the use of dental pulp cells for tissue regeneration. Deletion of sclerostin improves the dentinogenesis regeneration, while its role in dental pulp senescence is unclear. We investigated the role of sclerostin in subculture-induced senescence of human dental pulp cells (HDPCs) and in the senescence-related decline of proliferation and odontoblastic differentiation.MethodsImmunohistochemical staining and qRT-PCR analyses were performed to examine the expression pattern of sclerostin in young (20–30-year-old) and senescent (45–80-year-old) dental pulps. HDPCs were serially subcultured until senescence, and the expression of sclerostin was examined by qRT-PCR analysis. HDPCs with sclerostin overexpression and knockdown were constructed to investigate the role of sclerostin in HDPCs senescence and senescence-related impairment of odontoblastic differentiation potential.ResultsBy immunohistochemistry and qRT-PCR, we found a significantly increased expression level of sclerostin in senescent human dental pulp compared with that of young human dental pulp. Additionally, elevated sclerostin expression was found in subculture-induced senescent HDPCs in vitro. By sclerostin overexpression and knockdown, we found that sclerostin promoted HDPCs senescence-related decline of proliferation and odontoblastic differentiation potential with increased expression of p16, p53 and p21 and downregulation of the Wnt signaling pathway.DiscussionThe increased expression of sclerostin is responsible for the decline of proliferation and odontoblastic differentiation potential of HDPCs during cellular senescence. Anti-sclerostin treatment may be beneficial for the maintenance of the proliferation and odontoblastic differentiation potentials of HDPCs.
Uncontrollable bleeding and bacterial infection are the two major challenges in treating hemorrhaging civilian and military traumas. Herein, a novel hemostatic material was designed by in situ growth of zinc imidazolate frameworks (ZIF-8) into a chitin sponge (CTS) for effective hemostasis and anti-infection. ZIF-8 nanocrystals were not only uniformly dispersed throughout the CTS but also firmly anchored onto CTS with a residual mass of over 94% after 10 min of sonication. The resultant composite sponge (ZIF-8−CTS) displayed a hierarchically porous structure with a high specific surface area (∼126.2 m 2 •g −1 ) and superhydrophilicity, accelerating blood absorption to concentrate blood cells and platelets to form a primary blood clot. Meanwhile, upon contact with blood, ZIF-8 nanocrystals could gradually release Zn 2+ to activate the blood coagulation cascade reactions. Benefiting from these two synergistic effects, ZIF-8−CTS exhibited superior hemostasis performance than the traditional hemostatic materials (cotton gauze and gelatin sponge) in the rat femoral artery and liver injury models. Furthermore, it displayed excellent cytocompatibility and hemocompatibility. Importantly, it had an outstanding bactericidal effect with antibacterial ratio of up to 100% for Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. These results demonstrated that ZIF-8−CTS is an excellent antibacterial hemostatic material with a high potential in clinical applications.
Sclerotic dentin is a natural self-protective barrier beneath non-carious cervical lesions (NCCLs), which are mainly induced by mechanical stress. Sclerostin is a mechanosensory protein and serves as an inhibitor of dentinogenesis. However, its function on mechanotransduction in dentine-pulp complex has not been elucidated yet. In this study, decreased sclerostin expression was detected in odontoblasts beneath NCCL-affected sclerotic dentin. Then human pulp-derived odontoblast-like cells (hOBs) were subjected to mechanical strain (MS) in vitro: the results showed that MS-induced upregulation of odontogenic differentiation markers (dentin sialophosphoprotein, osteopontin, osteocalcin, and runt-related transcription factor 2) in hOBs with downregulated sclerostin expression, and this inductive differentiation was attenuated when sclerostin was overexpressed. Additionally, MS activated ERK1/2 pathway and ERK1/2 inhibition restored MS-induced downregulation of sclerostin. Proteasome inhibitor MG132 could also rescue MS-induced decrease of sclerostin. Furthermore, MS suppressed STAT3 pathway, which could be reversed by sclerostin overexpression. STAT3 inhibition was shown to ameliorate the reduction of odontogenic markers induced by sclerostin overexpression. Taken together, we conclude that MS downregulates sclerostin expression via the ERK1/2 and proteasome signaling pathways to promote odontogenic differentiation of hOBs through the STAT3 signaling pathway. It can therefore be inferred that under mechanical stress, sclerostin inhibition promotes reactive dentin formation by enhancing odontogenic differentiation of odontoblasts, which might be one of potential forming mechanisms of sclerotic dentin beneath NCCLs. K E Y W O R D SERK1/2, mechanotransduction, proteasome pathway, sclerostin, sclerotic dentin, SOST, STAT3
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.