Project description:We profiled miRNAs in gingival crevicular fluid (GCF) by a PCR-based method that yielded quantitative measures of more than 600 miRNAs. We found that miRNA profiles in GCF of periodontitis patients are distinct from those of healthy controls.
Project description:The human gingival crevicular fluid proteome and metaproteome of periodontitis are investigated, to shed light on the factors that mediate the host-microbiota interactions in the pathogenesis of periodontitis.
Project description:Fatty acid synthase (FASN) catalyzes key steps in de novo lipogenesis and has been implicated in inflammatory and metabolic disorders. Here we show that FASN expression is elevated in gingival tissues from aged individuals and patients with periodontitis. Using a ligature-induced periodontitis (LIP) model, pharmacological inhibition of FASN with C75 attenuated alveolar bone loss, reduced inflammatory cytokines and cell death in gingival crevicular fluid, and suppressed NLRP3 inflammasome activation in gingival tissues. Mechanistically, FASN inhibition led to substrate availability for NLRP3 palmitoylation, selectively impairing its interaction with ASC and consequently disrupting inflammasome assembly. Furthermore, enhanced palmitoylated NLRP3 was detected in gingival tissues upon LIP induction, also under obese-prone conditions, suggesting a novel disease-associated modification. Collectively, these findings uncover a previously unrecognized FASN–NLRP3 palmitoylation axis that regulates inflammasome activation in periodontitis and its associated high-risk metabolic states. Therapeutic targeting FASN may thus offer a promising strategy to ameliorate inflammasome-driven inflammation in periodontitis and its complications.
Project description:Fatty acid synthase (FASN) catalyzes key steps in de novo lipogenesis and has been implicated in inflammatory and metabolic disorders. Here we show that FASN expression is elevated in gingival tissues from aged individuals and patients with periodontitis. Using a ligature-induced periodontitis (LIP) model, pharmacological inhibition of FASN with C75 attenuated alveolar bone loss, reduced inflammatory cytokines and cell death in gingival crevicular fluid, and suppressed NLRP3 inflammasome activation in gingival tissues. Mechanistically, FASN inhibition led to substrate availability for NLRP3 palmitoylation, selectively impairing its interaction with ASC and consequently disrupting inflammasome assembly. Furthermore, enhanced palmitoylated NLRP3 was detected in gingival tissues upon LIP induction, also under obese-prone conditions, suggesting a novel disease-associated modification. Collectively, these findings uncover a previously unrecognized FASN–NLRP3 palmitoylation axis that regulates inflammasome activation in periodontitis and its associated high-risk metabolic states. Therapeutic targeting FASN may thus offer a promising strategy to ameliorate inflammasome-driven inflammation in periodontitis and its complications.
Project description:Inflammatory periodontal disease (periodontitis) is widespread in dogs. This study aimed to evaluate site-specific changes in the canine gingival crevicular fluid (GCF) proteome during the longitudinal progression from very mild gingivitis to mild periodontitis. Periodontitis diagnosis in dogs requires anaesthesia, our ultimate aim was to develop a periodontitis diagnostic that could be applied to samples taken from conscious dogs. The objective of this work was to identify potential biomarkers of periodontal disease progression in the GCF of dogs.
Project description:Saliva, gingival crevicular fluid (GCF), and serum are common sources for studying host response and oral microbiota in periodontal patients. This cross-sectional study aimed to compare the proteomic signatures of periodontitis patients using full-mouth periodontal sampling with those obtained from serum and saliva samples. This study analysed proteome profiles from these biological sources in three systemically healthy, non-smoking patients with stage III, and grade C periodontitis.
Project description:Aim: To provide an exploratory proteomic characterization of periodontal disease-related immune pathways by analyzing gingival crevicular fluid, revealing subtle proteomic changes accompanying disease progression. Materials and methods: Gingival crevicular fluid samples were collected from normal (control group), gingivitis, and periodontitis cohorts. Seventy-two samples were investigated, including those from normal (n=12), gingivitis (n=30) and periodontitis (n=30) groups. Samples were analyzed using liquid chromatography–mass spectrometry and sequential statistical analyses including differential expression, weighted gene co-expression network analysis, and protein–protein interaction networks, evaluated with receiver operating characteristic curve analyses. Results: We identified 649 proteins. Differential expression analysis revealed several regulated proteins, including RAC2, S100A12, and LCN2, in the periodontitis group. Weighted gene co‐expression network analysis clustered six protein modules: M1 module was enriched in complement proteins and prominent in gingivitis, whereas neutrophil-related M2 and M5 modules were correlated with periodontitis severity. Protein–protein interaction network analyses revealed hub proteins, including RAC2 and S100A12, highlighting their functional associations. Receiver operating characteristic analysis supported their within-cohort discriminatory potential for selected proteins. Conclusion: This exploratory study suggested the pathophysiological differences in proteome between gingivitis and periodontitis, establishing a foundation for future investigations and hypothesis-driven research.
Project description:This study evaluated the subgingival proteome of parents with periodontitis and their offspring, thereby assessing signatures of periodontal disease. Forty participants were allocated into four groups (n = 10 per group): parents with periodontitis (PP) and their offspring (CP), and control parents (PC) and their offspring (CC). Periodontal clinical parameters were assessed. Gingival crevicular fluid (GCF) and subgingival biofilm were collected from the same sites. Proteome from GCF were investigated by liquid chromatography-tandem mass spectrometry with data-independent acquisition (DIA-PASEF).
Project description:Complement inhibition has been successfully used to treat periodontitis in animal models. However, proteome studies that investigated the role of complement C3 were missing. The objective of this study was to characterize local tissue exudate (“gingival crevicular fluid”; GCF) changes after administration of a potent C3 inhibitor (Cp40, also known as AMY-101) to cynomolgus monkeys (Macaca fascicularis) with established periodontitis. Cp40 was administered locally in the maxillary gingival tissue either once per week (n=5 animals) or three times per week (n=10 animals), for six weeks followed by another six weeks of observation in the absence of treatment. The GCF were collected for liquid chromatography–mass spectrometry analysis (LC-MS/MS).