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Journal of Bone and Mineral Research :... Oct 2023Mouse ligature-induced periodontitis (LIP) has been used to study bone loss in periodontitis. However, the role of osteocytes in LIP remains unclear. Furthermore, there...
Mouse ligature-induced periodontitis (LIP) has been used to study bone loss in periodontitis. However, the role of osteocytes in LIP remains unclear. Furthermore, there is no consensus on the choice of alveolar bone parameters and time points to evaluate LIP. Here, we investigated the dynamics of changes in osteoclastogenesis and bone volume (BV) loss in LIP over 14 days. Time-course analysis revealed that osteoclast induction peaked on days 3 and 5, followed by the peak of BV loss on day 7. Notably, BV was restored by day 14. The bone formation phase after the bone resorption phase was suggested to be responsible for the recovery of bone loss. Electron microscopy identified bacteria in the osteocyte lacunar space beyond the periodontal ligament (PDL) tissue. We investigated how osteocytes affect bone resorption of LIP and found that mice lacking receptor activator of NF-κB ligand (RANKL), predominantly in osteocytes, protected against bone loss in LIP, whereas recombination activating 1 (RAG1)-deficient mice failed to resist it. These results indicate that T/B cells are dispensable for osteoclast induction in LIP and that RANKL from osteocytes and mature osteoblasts regulates bone resorption by LIP. Remarkably, mice lacking the myeloid differentiation primary response gene 88 (MYD88) did not show protection against LIP-induced bone loss. Instead, osteocytic cells expressed nucleotide-binding oligomerization domain containing 1 (NOD1), and primary osteocytes induced significantly higher Rankl than primary osteoblasts when stimulated with a NOD1 agonist. Taken together, LIP induced both bone resorption and bone formation in a stage-dependent manner, suggesting that the selection of time points is critical for quantifying bone loss in mouse LIP. Pathogenetically, the current study suggests that bacterial activation of osteocytes via NOD1 is involved in the mechanism of osteoclastogenesis in LIP. The NOD1-RANKL axis in osteocytes may be a therapeutic target for bone resorption in periodontitis. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Animals; Osteocytes; Periodontitis; RANK Ligand; Bone Resorption; Mice; Osteoclasts; Mice, Inbred C57BL; Ligation; Osteogenesis; Male
PubMed: 37551879
DOI: 10.1002/jbmr.4897 -
Clinical Oral Investigations Feb 2024We investigated the association between dietary flavonoids intake and periodontitis.
OBJECTIVES
We investigated the association between dietary flavonoids intake and periodontitis.
MATERIALS AND METHODS
This cross-sectional study analyzed data from the US National Health and Nutrition Examination Survey 2009-2010 on 3025 participants aged between 30 and 80 years who had full-mouth periodontal examination and dietary flavonoids intake data. This study used periodontal pocket depth (PPD) and clinical attachment loss (CAL) as periodontitis markers. Data were analyzed using multivariate linear regression.
RESULTS
After adjusting confounders, the middle tertile of total dietary flavonoids was associated with decreased mean PPD (0.06 mm, P = 0.016) and mean CAL (0.13 mm, P = 0.001) and the top tertile of total dietary flavonoids was significantly associated with decreases in mean PPD (0.05 mm, P = 0.029) and mean CAL (0.11 mm, P = 0.010). Both the middle and top tertiles of total flavonoids intake were significantly related with decreased mean CAL in females, those flossing 0 days/week, overweight and non-diabetic population but not in males, smokers, those flossing 1-6 days/week and diabetic population. Higher anthocyanidins, flavones and flavonols intake was significantly associated with decreased mean PPD and mean CAL while higher flavanones intake was only significantly associated with decreased mean CAL. Higher anthocyanidins intake was particularly related with greatest decreases in mean CAL (top tertile: 0.22 mm, middle tertile: 0.17 mm, both P < 0.010). However, no significant associations were found between isoflavones and flavan_3_ols intake and mean CAL.
CONCLUSIONS
Higher dietary flavonoids intake may be beneficial for periodontal health.
CLINICAL RELEVANCE
Additional anthocyanidins, flavanones, flavones and flavonols intake was associated with improved periodontal health.
Topics: Male; Female; Humans; Adult; Middle Aged; Aged; Aged, 80 and over; Cross-Sectional Studies; Nutrition Surveys; Anthocyanins; Periodontitis; Flavonoids; Polyphenols; Flavones; Flavanones; Flavonols
PubMed: 38396151
DOI: 10.1007/s00784-024-05561-1 -
Biological effects of IL-33/ST2 axis on oral diseases: autoimmune diseases and periodontal diseases.International Immunopharmacology Sep 2023IL-33 is a relatively new member of the IL-1 cytokine family, which plays a unique role in autoimmune diseases, particularly some oral diseases dominated by immune... (Review)
Review
IL-33 is a relatively new member of the IL-1 cytokine family, which plays a unique role in autoimmune diseases, particularly some oral diseases dominated by immune factors. The IL-33/ST2 axis is the main pathway by which IL-33 signals affect downstream cells to produce an inflammatory response or tissue repair. As a newly discovered pro-inflammatory cytokine, IL-33 can participate in the pathogenesis of autoimmune oral diseases such as Sjogren's syndrome and Behcet's disease. Moreover, the IL-33/ST2 axis also recruits and activates mast cells in periodontitis, producing inflammatory chemokines and mediating gingival inflammation and alveolar bone destruction. Interestingly, the high expression of IL-33 in the alveolar bone, which exhibits anti-osteoclast effects under appropriate mechanical loading, also confirms its dual role of destruction and repair in an immune-mediated periodontal environment. This study reviewed the biological effects of IL-33 in autoimmune oral diseases, periodontitis and periodontal bone metabolism, and elaborated its potential role and impact as a disease enhancer or a repair factor.
Topics: Humans; Interleukin-33; Interleukin-1 Receptor-Like 1 Protein; Periodontitis; Autoimmune Diseases; Cytokines
PubMed: 37393839
DOI: 10.1016/j.intimp.2023.110524 -
Community Dentistry and Oral... Aug 2024Over the years, several reviews of periodontal risk assessment tools have been published. However, major misunderstandings still prevail in repeated attempts to use... (Review)
Review
Over the years, several reviews of periodontal risk assessment tools have been published. However, major misunderstandings still prevail in repeated attempts to use these tools for prognostic risk prediction. Here we review the principles of risk prediction and discuss the value and the challenges of using prediction models in periodontology. Most periodontal risk prediction models have not been properly developed according to guidance given for the risk prediction model development. This shortcoming has led to several problems, including the creation of arbitrary risk scores. These scores are often labelled as 'high risk' without explicit boundaries or thresholds for the underlying continuous risk estimates of patient-important outcomes. Moreover, it is apparent that prediction models are often misinterpreted as causal models by clinicians and researchers although they cannot be used as such. Additional challenges like the critical assessment of transportability and applicability of these prediction models, as well as their impact on clinical practice and patient outcomes, are not considered in the literature. Nevertheless, these instruments are promoted with claims regarding their ability to deliver more individualized and precise periodontitis treatment and prevention, purportedly resulting in improved patient outcomes. However, people with or without periodontitis deserve proper information about their risk of developing patient-important outcomes such as tooth loss or pain. The primary objective of disseminating such information should not be to emphasize assumed treatment efficacy, hype individualization of care, or promote business interests. Instead, the focus should be on providing individuals with locally validated and regularly updated predictions of specific risks based on readily accessible and valid key predictors (e.g. age and smoking).
Topics: Humans; Risk Assessment; Periodontal Diseases; Prognosis; Periodontitis; Risk Factors
PubMed: 38243665
DOI: 10.1111/cdoe.12942 -
ELife Mar 2024Periodontitis drives irreversible destruction of periodontal tissue and is prone to exacerbating inflammatory disorders. Systemic immunomodulatory management continues...
Periodontitis drives irreversible destruction of periodontal tissue and is prone to exacerbating inflammatory disorders. Systemic immunomodulatory management continues to be an attractive approach in periodontal care, particularly within the context of 'predictive, preventive, and personalized' periodontics. The present study incorporated genetic proxies identified through genome-wide association studies for circulating immune cells and periodontitis into a comprehensive Mendelian randomization (MR) framework. Univariable MR, multivariable MR, subgroup analysis, reverse MR, and Bayesian model averaging (MR-BMA) were utilized to investigate the causal relationships. Furthermore, transcriptome-wide association study and colocalization analysis were deployed to pinpoint the underlying genes. Consequently, the MR study indicated a causal association between circulating neutrophils, natural killer T cells, plasmacytoid dendritic cells, and an elevated risk of periodontitis. MR-BMA analysis revealed that neutrophils were the primary contributors to periodontitis. The high-confidence genes and , located on 1q21.3, could potentially serve as immunomodulatory targets for neutrophil-mediated periodontitis. These findings hold promise for early diagnosis, risk assessment, targeted prevention, and personalized treatment of periodontitis. Considering the marginal association observed in our study, further research is required to comprehend the biological underpinnings and ascertain the clinical relevance thoroughly.
Topics: Humans; Bayes Theorem; Genome-Wide Association Study; Periodontitis; Calgranulin B; Dendritic Cells
PubMed: 38536078
DOI: 10.7554/eLife.92895 -
Journal of Periodontal Research Dec 2023The aim of this study was to investigate metabolomics markers in the saliva of patients with periodontal health, gingivitis and periodontitis.
OBJECTIVE
The aim of this study was to investigate metabolomics markers in the saliva of patients with periodontal health, gingivitis and periodontitis.
BACKGROUND
The use of metabolomics for diagnosing and monitoring periodontitis is promising. Although several metabolites have been reported to be altered by inflammation, few studies have examined metabolomics in saliva collected from patients with different periodontal phenotypes.
METHODS
Saliva samples collected from a total of 63 patients were analysed by nuclear magnetic resonance (NMR) followed by ELISA for interleukin (IL)-1β. The patient sample, well-characterised clinically, included periodontal health (n = 8), gingivitis (n = 19) and periodontitis (n = 36) cases, all non-smokers and not diabetic.
RESULTS
Periodontal diagnosis (healthy/gingivitis/periodontitis) was not associated with any salivary metabolites in this exploratory study. Periodontal staging showed nominal associations with acetoin (p = .030) and citrulline (p = .047). Among other investigated variables, the use of systemic antibiotics in the previous 3 months was associated with higher values of the amino acids taurine, glycine and ornithine (p = .002, p = .05 and p = .005, respectively, at linear regression adjusted for age, gender, ethnicity, body mass index and staging).
CONCLUSION
While periodontal staging was marginally associated with some salivary metabolites, other factors such as systemic antibiotic use may have a much more profound effect on the microbial metabolites in saliva. Metabolomics in periodontal disease is still an underresearched area that requires further observational studies on large cohorts of patients, aiming to obtain data to be used for clinical translation.
Topics: Humans; Saliva; Periodontitis; Gingivitis; Periodontal Diseases; Biomarkers
PubMed: 37787434
DOI: 10.1111/jre.13183 -
Immunological link between periodontitis and type 2 diabetes deciphered by single-cell RNA analysis.Clinical and Translational Medicine Dec 2023Type 2 diabetes mellitus (DM) is a complex metabolic disorder that causes various complications, including periodontitis (PD). Although a bidirectional relationship has...
BACKGROUND
Type 2 diabetes mellitus (DM) is a complex metabolic disorder that causes various complications, including periodontitis (PD). Although a bidirectional relationship has been reported between DM and PD, their immunological relationship remains poorly understood. Therefore, this study aimed to compare the immune response in patients with PD alone and in those with both PD and DM (PDDM) to expand our knowledge of the complicated connection between PD and DM.
METHODS
Peripheral blood mononuclear cells were collected from 11 healthy controls, 10 patients with PD without DM, and six patients with PDDM, followed by analysis using single-cell RNA sequencing. The differences among groups were then compared based on intracellular and intercellular perspectives.
RESULTS
Compared to the healthy state, classical monocytes exhibited the highest degree of transcriptional change, with elevated levels of pro-inflammatory cytokines in both PD and PDDM. DM diminished the effector function of CD8+ T and natural killer (NK) cells as well as completely modified the differentiation direction of these cells. Interestingly, a prominent pathway, RESISTIN, which is known to increase insulin resistance and susceptibility to diabetes, was found to be activated under both PD and PDDM conditions. In particular, CAP1+ classical monocytes from patients with PD and PDDM showed elevated nuclear factor kappa B-inducing kinase activity.
CONCLUSIONS
Overall, this study elucidates how the presence of DM contributes to the deterioration of T/NK cell immunity and the immunological basis connecting PD to DM.
Topics: Humans; Diabetes Mellitus, Type 2; Leukocytes, Mononuclear; Periodontitis; Cytokines; Killer Cells, Natural
PubMed: 38082425
DOI: 10.1002/ctm2.1503 -
International Journal of Molecular... Dec 2023Rheumatoid arthritis (RA) and periodontitis are chronic inflammatory diseases that widely spread and share the same patterns of pro-inflammatory cytokines. This... (Review)
Review
Rheumatoid arthritis (RA) and periodontitis are chronic inflammatory diseases that widely spread and share the same patterns of pro-inflammatory cytokines. This systematic review aims to evaluate the effects of non-surgical periodontal treatment (NSPT) on RA and, conversely, the impact of disease-modifying anti-rheumatic drugs (DMARDs) on periodontitis. PubMed, Embase, and Web of Science were searched using the MESH terms "periodontitis" and "rheumatoid arthritis" from January 2012 to September 2023. A total of 49 articles was included in the final analysis, 10 of which were randomized controlled trials. A total of 31 records concerns the effect of NSPT on parameters of RA disease activity, including a 28-joint disease activity score, anti-citrullinated protein antibodies, rheumatoid factor, C reactive protein, erythrocyte sedimentation rate, pro-inflammatory cytokines and acute phase proteins in serum, saliva, gingival crevicular fluid, and synovial fluid. A total of 18 articles investigated the effect of DMARDs on periodontal indexes and on specific cytokine levels. A quality assessment and risk-of-bias of the studies were also performed. Despite some conflicting results, there is evidence that RA patients and periodontitis patients benefit from NSPT and DMARDs, respectively. The limitations of the studies examined are the small samples and the short follow-up (usually 6 months). Further research is mandatory to evaluate if screening and treatment of periodontitis should be performed systematically in RA patients, and if the administration of DMARDs is useful in reducing the production of cytokines in the periodontium.
Topics: Humans; Antirheumatic Agents; Periodontitis; Arthritis, Rheumatoid; Rheumatoid Factor; Cytokines
PubMed: 38139057
DOI: 10.3390/ijms242417228 -
Journal of Periodontal Research Dec 2023To evaluate the prognostic accuracy of microbial biomarkers and their associations with the response to active periodontal treatment (APT) and supportive periodontal... (Review)
Review
To evaluate the prognostic accuracy of microbial biomarkers and their associations with the response to active periodontal treatment (APT) and supportive periodontal therapy (SPT). Microbial dysbiosis plays a crucial role in the disease processes of periodontitis. Biomarkers based on microbial composition may offer additional prognostic value, supplementing the limitations of current clinical parameters. While these microbial biomarkers have been clinically evaluated, there is a lack of consensus regarding their prognostic accuracy. A structured search strategy was applied to MEDLINE (PubMed), Cochrane Library, and Embase on 1/11/2022 to identify relevant publications. Prospective clinical studies involving either APT or SPT, with at least 3-month follow-up were included. There were no restrictions on the type of microbial compositional analysis. 1918 unique records were retrieved, and 13 studies (comprising 943 adult patients) were included. Heterogeneity of the studies precluded a meta-analysis, and none of the included studies had performed the sequence analysis of the periodontal microbiome. Seven and six studies reported on response to APT and SPT, respectively. The prognostic accuracy of the microbial biomarkers for APT and SPT was examined in only two and four studies, respectively. Microbial biomarkers had limited predictive accuracy for APT and inconsistent associations for different species across studies. For SPT, elevated abundance of periodontal pathogens at the start of SPT was predictive of subsequent periodontal progression. Similarly, persistent high pathogen loads were consistently associated with progressive periodontitis, defined as an increased pocket probing depth or clinical attachment loss. While there was insufficient evidence to support the clinical use of microbial biomarkers as prognostic tools for active periodontal treatment outcomes, biomarkers that quantify periodontal pathogen loads may offer prognostic value for predicting progressive periodontitis in the subsequent supportive periodontal therapy phase. Additional research will be required to translate information regarding subgingival biofilm composition and phenotype into clinically relevant prognostic tools.
Topics: Adult; Humans; Prospective Studies; Periodontitis; Treatment Outcome; Prognosis; Biomarkers
PubMed: 37724467
DOI: 10.1111/jre.13188 -
Journal of Periodontal Research Apr 2024Numerous studies have proposed that periodontitis is a potential risk factor for Alzheimer's disease. However, the association between periodontitis and brain normal...
BACKGROUND
Numerous studies have proposed that periodontitis is a potential risk factor for Alzheimer's disease. However, the association between periodontitis and brain normal cognition in aged and elderly individuals (NCs) is unclear. Such a link could provide clues to Alzheimer's disease development and strategies for early prevention.
OBJECTIVE
To explore the associations between periodontal condition and metrics of both brain structure and function among NCs with the help of multimodal magnetic resonance imaging (MRI).
METHODS
High-resolution T1-weighted structural data, resting-state functional-MRI data, and measures of periodontal condition were collected from 40 NCs. Cortical volume, thickness, and area as well as regional homogeneity were calculated with the aid of DPABISurf software. Correlation analyses were then conducted between each imaging metric and periodontal index.
RESULTS
Consistent negative correlations were observed between severity of periodontitis (mild, moderate, severe) and cortical volume, area, and thickness, not only in brain regions that took charge of primary function but also in brain regions associated with advanced cognition behavior. Among participants with mild attachment loss (AL) and a shallow periodontal pocket depth (PPD), periodontal index was positively correlated with most measures of brain structure and function, while among participants with severe AL and deep PPD, periodontal index was negatively correlated with measures of brain structure and function (all p < .005 for each hemisphere).
CONCLUSIONS
Our results demonstrate that periodontitis is associated with widespread changes in brain structure and function among middle-aged and elderly adults without signs of cognitive decline, which might be a potential risk factor for brain damage.
Topics: Aged; Adult; Middle Aged; Humans; Alzheimer Disease; Periodontitis; Cognition; Brain; Periodontal Diseases
PubMed: 38014515
DOI: 10.1111/jre.13214