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Ulcerative colitis aggravates periodontitis via myeloid skewing of hematopoietic progenitor cell differentiation

ABSTRACT: Objective Ulcerative colitis (UC) is a risk factor of periodontitis. This study aimed to investigate whether hematopoietic stem and progenitor cells (HSPCs) and their myeloid progeny exacerbate periodontal inflammation in UC. Design Ligature-induced periodontitis (LIP) was established in dextran sulfate sodium (DSS)-induced colitis (DIC) C57BL/6 mice. The bone resorption, intestinal and periodontal inflammation were evaluated by micro-CT and histological analyses. Inflammatory cytokines and lipopolysaccharide (LPS) in serum and gut microbiota were assessed by multiplexed flow cytometric assay, ELISA and 16S rRNA sequencing, respectively. Flow cytometry was performed to analyze HSPCs differentiation, and to sort hematopoietic stem cells for transcriptomic analysis. Berberine treatment of DIC was employed to investigate whether dampening of DIC would alleviate periodontitis. Results DIC mice exhibited disrupted intestinal barrier with dysbiotic gut microbiota, corroborating the elevated serum level of LPS and IL-1. Compared to DIC-free/LIP mice, DIC/LIP mice showed aggravated alveolar bone resorption, with enrichment of neutrophils extracellular traps (NETs) in periodontal tissues. DIC promoted myelopoiesis of HSPCs by up-regulating myeloid differentiation pathway. Intragastric administration of berberine dampened DIC and rescued the myeloid skewing of HSPCs, consequently alleviating periodontal destruction. Intriguingly, LIP induction after DIC remission still exhibited aggravated periodontal destruction and myeloid skewing of HSPCs, indicating a UC-trained immunity against periodontal infection. Conclusion Increased gut permeability and microbial dysbiosis in UC elevate the serum level of LPS and IL-1, inducing myeloid skewing of HSPCs with an immune memory. Generation of inflammatory potential myeloid cells causes NETs accumulation and aggravates periodontal destruction in the UC-related periodontitis.

ORGANISM(S): Mus musculus

PROVIDER: GSE249582 | GEO | 2023/12/10

REPOSITORIES: GEO

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Project description:Periodontitis (PD) as a chronic inflammatory disease instigated by periodontal pathogenic bacteria and mediated by the host immune response, resulting in the destruction of supporting periodontal tissue and tooth loss in adults. Constructing an injectable delivery system that allows for sustained drug release within periodontal pockets to continuously eliminate pathogenic bacteria, reduce periodontal inflammation, and promote periodontal tissue regeneration is an effective strategy for periodontitis treatment. Here, we explore the therapeutic potential and underlying mechanisms of curcumin-loaded Pickering emulsion (PE-CUR) in periodontitis treatment. The Pickering emulsion formulation offers an effective delivery system, enhancing curcumin's bioavailability and therapeutic efficacy. In vitro studies, we demonstrate that the PE-CUR exhibit excellent biocompatibility and anti-inflammatory property by elimination of reactive oxygen species (ROS). In addition, PE-CUR significantly eliminate key periodontal pathogens, including Porphyromonas gingivalis (P. gingivalis) and Staphylococcus aureus (S. aureus). In a rat model of periodontitis, PE-CUR significantly attenuates periodontal tissue inflammation and alveolar bone loss, indicating a protective effect against periodontal tissue destruction. Mechanistically, PE-CUR promotes the expression of anti-inflammatory factors and inhibits the release of pro-inflammatory factors by regulating macrophage polarization from M1 to M2 and modulating the MAPK and PI3K-AKT signaling pathway. Furthermore, PE-CUR decreases the formation of osteoclasts as well as stimulates the activation and differentiation of osteoblasts successively, thereby ameliorating the periodontal inflammation and promoting the alveolar bone regeneration. Overall, our findings elucidate the therapeutic mechanisms of PE-CUR in periodontitis, suggesting its potential as a promising treatment strategy warranting further clinical investigation.

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Ulcerative colitis aggravates periodontitis via myeloid skewing of hematopoietic progenitor cell differentiation

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