Progression Of Periodontitis Research Articles

Shotgun metagenomic analysis of the oral microbiome in gingivitis: a nested case-control study

ABSTRACT Background Gingivitis, i.e. inflammation of the gums, is often induced by dental plaque. However, its exact link to the oral microbiota remains unclear. Methods In a case-control study involving 120 participants, comprising 60 cases and 60 controls (mean age (SD) 36.6 (7.6) years; 50% males), nested within a prospective multicentre cohort study, we examined the oral microbiome composition of gingivitis patients and their controls using shotgun metagenomic sequencing of saliva samples. Participants underwent clinical and radiographic oral health examinations, including bleeding on probing (BOP), at six tooth sites. BOP ≥33% was considered ‘generalized gingivitis/initial periodontitis’(GG/IP), and BOP <33% as ‘healthy and localized gingivitis’(H/LG). Functional potential was inferred using HUMANn3. Results GG/IP exhibited an increase in the abundance of Actinomyces, Porphyromonas, Aggregatibacter, Corynebacterium, Olsenella, and Treponema, whereas H/LG exhibited an increased abundance of Candidatus Nanosynbacter. Nineteen bacterial species and four microbial functional profiles, including L-methionine, glycogen, and inosine-5’-phosphate biosynthesis, were associated with GG/IP. Constructing models with multiple markers resulted in a strong predictive value for GG/IP, with an area under the curve (ROC) of 0.907 (95% CI: 0.848-0.966). Conclusion We observed distinct differences in the oral microbiome between the GG/IP and H/LG groups, indicating similar yet unique microbial profiles and emphasizing their potential role in progression of periodontal diseases.

Effects of e-cigarette smoking on periodontal health: A scoping review.

Use of electronic cigarettes (ECs), also known as vaping, has gained remarkable popularity globally during the last decade especially among young people. Current evidence suggests that vaping may be associated with health risks. The aim of this study is to evaluate whether vaping increases the risk for initiation and progression of periodontal disease; and to appraise the clinical changes seen in patients using e-cigarettes, and how these changes impact the management of periodontal disease. A comprehensive electronic search was conducted on the PubMed, Scopus and Embase databases using the following search terms: Electronic Cigarettes OR vaping OR electronic nicotine delivery systems OR e-cigarettes AND Periodontitis. The search was limited to studies published from 1st January 2012 to 31st December 2022. A total of 23 clinical studies focusing on the effect of e-cigarette smoking on the periodontal clinical parameters, levels of inflammatory mediators, alteration in periodontal microflora, and response to periodontal treatment were found to be eligible for inclusion in the review. Vaping may be associated with greater clinical attachment loss (CAL) compared to non-smokers. Moreover, ECs are also associated with unfavorable effects on periodontal microbial counts, biomarkers of inflammation and oxidative stress. Vaping may play a role in the initiation and progression of periodontal disease by altering the host response resulting in the release of inflammatory cytokines and periodontal microflora. Clinical studies show deleterious effects of vaping on periodontal health as well as less favourable response to periodontal treatment is observed in e-cigarette users compared to non-smokers. However, compared to cigarette smoking, the effects of vaping are less remarkable.

Melatonin Decreases Alveolar Bone Loss in Rats with Experimental Periodontitis and Osteoporosis: A Morphometric and Histopathologic Study.

Periodontitis and post-menopausal osteoporosis include common chronic bone disorders worldwide, with similar etiopathogenetic events. This study evaluated the effect of systemic melatonin administration on the alveolar bone destruction of periodontitis progression in an experimental periodontitis model in osteoporotic rats. Forty-four Wistar rats were randomly divided into six experimental groups: control (C; n = 6); osteoporosis (O; n = 6); ligated periodontitis (LP; n = 8); osteoporosis- and periodontitis-induced (O+LP; n = 8); osteoporosis- and periodontitis-induced through 30 mg/kg/day melatonin administration (ML30; n = 8); and osteoporosis- and periodontitis-induced through 50 mg/kg/day melatonin administration (ML50; n = 8). The rats underwent bilateraloophorectomy and were maintained for 4 months to induce osteoporosis. After 4 months, 4-0 silk ligatures were placed submarginally around the mandibular first molar of each rat to induce experimental periodontitis, and melatonin was administered in the ML30 and ML50 groups for 30 days. Changes in alveolar bone levels were clinically measured, and tissues were histopathologically examined. Osteoclastic activity in the LP and O+LP groups was significantly higher than in the other groups (p < 0.05), but was similar in the C, O, and ML30 groups (p > 0.05). RANKL activity was the highest in the O+LP group, while melatonin decreased RANKL activity in the melatonin-administered groups (p < 0.05). Systemically administered melatonin significantly decreased alveolar bone loss in the ML30 and ML50 groups compared with that in the periodontitis groups (p < 0.05). Melatonin inhibited alveolar bone destruction by decreasing the RANKL expression and inflammatory cell infiltration and increased osteoblastic activity in a rat model with osteoporosis and periodontitis.

Single-Index Mixed-Effects Model for Asymmetric Bivariate Clustered Data

Studies/trials assessing status and progression of periodontal disease (PD) usually focus on quantifying the relationship between the clustered (tooth within subjects) bivariate endpoints, such as probed pocket depth (PPD), and clinical attachment level (CAL) with the covariates. Although assumptions of multivariate normality can be invoked for the random terms (random effects and errors) under a linear mixed model (LMM) framework, violations of those assumptions may lead to imprecise inference. Furthermore, the response-covariate relationship may not be linear, as assumed under a LMM fit, and the regression estimates obtained therein do not provide an overall summary of the risk of PD, as obtained from the covariates. Motivated by a PD study on Gullah-speaking African-American Type-2 diabetics, we cast the asymmetric clustered bivariate (PPD and CAL) responses into a non-linear mixed model framework, where both random terms follow the multivariate asymmetric Laplace distribution (ALD). In order to provide a one-number risk summary, the possible non-linearity in the relationship is modeled via a single-index model, powered by polynomial spline approximations for index functions, and the normal mixture expression for ALD. To proceed with a maximum-likelihood inferential setup, we devise an elegant EM-type algorithm. Moreover, the large sample theoretical properties are established under some mild conditions. Simulation studies using synthetic data generated under a variety of scenarios were used to study the finite-sample properties of our estimators, and demonstrate that our proposed model and estimation algorithm can efficiently handle asymmetric, heavy-tailed data, with outliers. Finally, we illustrate our proposed methodology via application to the motivating PD study.

Regulation of the AGEs-induced inflammatory response in human periodontal ligament cells via the AMPK/NF-κB/ NLRP3 signaling pathway

The heightened prevalence and accelerated progression of periodontitis in individuals with diabetes is primarily attributed to inflammatory responses in human periodontal ligament cells (HPDLCs). This study is aimed at delineating the regulatory mechanism of nucleotide-binding oligomerization domain-like receptors (NLRs) in mediating inflammation incited by muramyl dipeptide (MDP) in HPDLCs, under the influence of advanced glycation end products (AGEs), metabolic by-products associated with diabetes. We performed RNA-seq in HPDLCs induced by AGEs treatment and delineated activation markers for the receptor of AGEs (RAGE). It showed that advanced glycation end products modulate inflammatory responses in HPDLCs by activating NLRP1 and NLRP3 inflammasomes, which are further regulated through the NF-κB signaling pathway. Furthermore, AGEs synergize with NOD2, NLRP1, and NLRP3 inflammasomes to augment MDP-induced inflammation significantly.

Antibacterial effect of green tea against Porphyromonas gingivalis: a literature review

Green tea is regarded as a healthy beverage due to the biological action of polyphenols, specifically catechins. Researchers investigated the inhibitory effects of green tea (Camellia sinensis) plant on both Gram- positive and Gram-negative bacteria. Periodontitis is mainly initiated when dysbiosis of the subgingival microbiome takes place. Porphyromonas gingivalis is one of the key pathogens involved in the initiation and progression of periodontitis when its levels in subgingival biofilm overwhelm the host's immune system. It is the main pathogen that is significantly linked to severe periodontal disease. In this study, details about P. gingivalis including information about its structure, virulence factors were provided. Next, Important points related to green tea, including its active ingredients and antibacterial activity, have been clarified. Finally, the objective of this study was to demonstrate how green tea has antibacterial effects on P. gingivalis.

Leukemia inhibitory factor protects against experimental periodontitis through immuno-modulations of both macrophages and periodontal ligament fibroblasts.

To explore the role of leukemia inhibitory factor (LIF) in periodontitis via in vivo and in vitro experiments. The second upper molar of LIF knockout mice and their wild-type littermates were ligated for 8 days. Micro-computed tomography (micro-CT), histological analysis, and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. The expression levels of proinflammatory cytokines were examined in mouse bone marrow derived macrophages and human periodontal ligament fibroblasts (HPDLFs) after lipopolysaccharide (LPS) treatment. LIF deficiency promoted alveolar bone loss, inflammatory cells infiltration, osteoclasts formation and collagen fiber degradation in ligature-induced mouse, along with higher expressions of proinflammatory cytokines, including interleukin-6 (IL6), IL-1β (IL1B), tumor necrosis factor-α (TNFA), matrix metalloproteinase 13 (MMP13), and RANKL/OPG ratio. Additionally, LIF deletion led to higher expression levels of these proinflammatory cytokines in mouse bone marrow-derived macrophages from both femur and alveolar bone and HPDLFs when treated with LPS. Administration of recombined LIF attenuated TNFA, IL1B, and RANKL/OPG ratio in HPDLFs. These findings indicate that LIF deficiency promotes the progress of periodontitis via modulating immuno-inflammatory responses of macrophages and periodontal ligament fibroblasts, and the application of LIF may be an adjunctive treatment for periodontitis to resolute inflammation.

Overview, Trends, and Collaboration on Immunization, Vaccination, and Immunomodulation Therapies for Periodontitis: A Scientometric Study.

To identify patterns and trends in the field of immunization, vaccination, and immunomodulation therapies for periodontitis. Metadata were collected from the Scopus database on publications related to these topics from January 1986 to February 2024. Several types of papers were included in this study, a total of 22 publications. Data were extracted from relevant publications and loaded into SciVal for analysis that were used to identify trends and patterns in the data, including cross-country collaboration, thematic evolution, and keyword distribution. Mohsen Amin of Tehran University of Medical Sciences in Iran and S. Aadil Ahamed and Annie Kitty George of Saveetha Institute of Medical and Technical Sciences in India were found to be notable contributors in this field. India leads in terms of academic paper production, followed by Iran and China. The journals Expert Review of Vaccines and International Immunopharmacology have published significant papers in this field. According to Lotka's Law, most authors have written only one paper, reflecting the distribution of productivity in many academic and scientific fields. Collaborations were observed between Iran and Canada, Korea and New Zealand, and the United States and Belgium. This study provides useful insight into the predominant trends and patterns in the scientific literature in the field of immunization, vaccination, and immunomodulation therapies for periodontitis. The findings of this study may help to understand the dynamics of the production on immunization, vaccination, and immunomodulation therapies could reduce the inflammation and progression of periodontitis, thus improving the patient's oral and overall health. How to cite this article: Mauricio F, Mendoza R, Silva H, et al. Overview, Trends, and Collaboration on Immunization, Vaccination, and Immunomodulation Therapies for Periodontitis: A Scientometric Study. J Contemp Dent Pract 2024;25(2):128-133.

Assessment of the Antibacterial Effect of Vitamin D3 against Red Complex Periodontal Pathogens: A Microbiological Assay.

The study aims is to evaluate the antibacterial effect of vitamin D3 against the red complex bacteria, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia in chronic periodontitis patients. The study comprised 98 participants with chronic periodontitis. All clinical parameters including plaque index (PI), gingival bleeding index (GBI), probing pocket depth (PPD), clinical attachment level (CAL), and a microbiological assay of P. gingivalis, T. denticola, T. forsythia were assessed at the baseline. All study participants who underwent scaling and root planning were divided into two groups, A and B, each with 49 patients and only group B patients were advised to take vitamin D supplementation of 60,000 IU granules, once daily for 2 months. All the patients of both the groups were recalled at the end of 2nd month and all the clinical and microbiological parameters were reassessed. After two months, there was a reduction in all the clinical markers in both groups, but the group B patients showed more improvement following non-surgical treatment vitamin D intake. There was also a statistical reduction in P. gingivalis, T. denticola, and T. forsythia following administration of vitamin D in group B patients compared to group A. These discoveries proposed that vitamin D has a superb antimicrobial impact against red complex periodontal microbes and might be considered a promising compound in the counteraction of periodontal disease. Vitamin D is considered to possess anti-inflammatory and antimicrobial activity, which may help to delay the progression of periodontitis. So, vitamin D3 can be used as a potential supplement that could be employed to stop the advancement of periodontal disease. How to cite this article: Govindharajulu R, Syed NK, Sukumaran B, et al. Assessment of the Antibacterial Effect of Vitamin D3 against Red Complex Periodontal Pathogens: A Microbiological Assay. J Contemp Dent Pract 2024;25(2):114-117.

Nlrp3 inflammasome drives regulatory T cell depletion to accelerate periapical bone erosion.

Apical periodontitis is an inflammatory disorder triggered by an immune response to bacterial infection, leading to the periapical tissue damage and alveolar resorption. However, the underlying mechanisms driving this process remain elusive, due to the complex and interconnected immune microenvironment within the local lesion site. In this study, the influence of Nlrp3 inflammasome-mediated immune response on the apical periodontitis was investigated. RNA sequencing, immunohistochemistry and ELISA assay were performed to investigate the activation of Nlrp3 inflammasome signalling pathways in the human periapical tissues, including radicular cysts, periapical granulomas and healthy oral mucosa. A mouse model of apical periodontitis was established to study the role of Nlrp3 knockout in periapical bone resorption and Treg cell stability, and the underlying mechanism was explored through invitro experiments. Invivo Treg cell adoptive transfer was performed to investigate the effects of Treg cells on the progression of apical periodontitis. Our findings find that the hyperactivated Nlrp3 inflammasome is present in human periapical lesions and plays a vital role in the immune-related periapical bone loss. Using a mouse model of apical periodontitis, we observe that Nlrp3 deficiency is resistant to bone resorption. This protection was accompanied by elevated generation and infiltration of local Treg cells that displayed a notable ability to suppress RANKL-dependent osteoclast differentiation. In terms of the mechanism of action, Nlrp3 deficiency directly inhibits the osteoclast differentiation and bone loss through JNK/MAPK and NF-κB pathways. In addition, Nlrp3 induces pyroptosis in the stem cells from apical papilla (SCAPs), and the subsequent release of cytokines affects the stability of Treg cell in periapical lesions, leading indirectly to enhanced bone resorption. In turn, adoptive transfer of both Nlrp3-deficient and wild-type Treg cells effectively prevent the bone erosion during apical periodontitis. Together, our data identify that the Nlrp3 inflammasome modulates the Treg cell stability and osteoclastogenesis in the periapical inflammatory microenvironment, thus determining the progression of bone erosion.

Imbalanced EphB4/EphrinB2 Signaling Modulates Bone Resorption in Periodontitis Induced by Porphyromonas gingivalis.

Periodontitis, a chronic infectious disease in periodontal tissues, is characterized by an imbalance of alveolar bone resorption and remodeling, which eventually results in tooth loosening and even tooth loss. The etiology of periodontitis is polymicrobial synergy and dysbiosis, in which Porphyromonas gingivalis (P. gingivalis) is one of the primary pathogens responsible for periodontitis progression. The interplay of EphrinB2/EphB4 is crucial for osteoblast-osteoclast communication during bone remodeling and healing. This study investigates the mechanism of EphB4/EphrinB2 transduction modulating osteogenesis inhibition and bone resorption in periodontitis induced by P. gingivalis. An in vivo model of chronic periodontitis provoked by P. gingivalis was constructed, the inflammation and bone resorption were evaluated. The expression of EphB4 and EphrinB2 proteins in periodontal tissues was detected, which was also evaluated, respectively, in osteoblasts and osteoclasts infected with P. gingivalis in vitro. Then, a simulated coculture model of osteoblasts and osteoclasts was established to activate the forward and reverse pathways of EphB4/EphrinB2 with P. gingivalis infection. This study showed that P. gingivalis infection promoted alveolar bone resorption in rats and enhanced EphB4 and EphrinB2 expression in periodontal tissues. EphB4 and molecules associated with osteogenesis in osteoblasts infected with P. gingivalis were inhibited, while EphrinB2 and osteoclast differentiation-related markers in osteoclasts were activated. In conclusion, this study suggested that EphB4/EphrinB2 proteins were involved in alveolar bone remodeling in the process of periodontitis induced by P. gingivalis infection. Moreover, attenuated EphB4/EphrinB2 with P. gingivalis infection weakened osteoblast activity and enhanced osteoclast activity.

Marginal clustered multistate models for longitudinal progressive processes with informative cluster size

AbstractInformative cluster size (ICS) is a phenomenon where cluster size is related to the outcome. While multistate models can be applied to characterize the unit‐level transition process for clustered interval‐censored data, there is a research gap addressing ICS within this framework. We propose two extensions of multistate model that account for ICS to make marginal inference: one by incorporating within‐cluster resampling and another by constructing cluster‐weighted score functions. We evaluate the performances of the proposed methods through simulation studies and apply them to the Veterans Affairs Dental Longitudinal Study (VADLS) to understand the effect of risk factors on periodontal disease progression. ICS occurs frequently in dental data, particularly in the study of periodontal disease, as people with fewer teeth due to the disease are more susceptible to disease progression. According to the simulation results, the mean estimates of the parameters obtained from the proposed methods are close to the true values, but methods that ignore ICS can lead to substantial bias. Our proposed methods for clustered multistate model are able to appropriately take ICS into account when making marginal inference of a typical unit from a randomly sampled cluster.

Pathogenic Features of Porphyromonas Gingivalis Influence Progression of Rheumatoid Arthritis

Abstract Autoimmune diseases, such as rheumatoid arthritis (RA), are examples of yet not entirely understood etiology. They are linked to immune system dysfunction, which becomes immunologically overactive, damaging the body’s tissues and organs. At least three major factors underlie the development of autoimmune disorders: environmental factors, including the oral and intestinal microbiomes, genetic predisposition, and aberrant autoimmune response. The dysbiosis of the oral microbiota, in particular, exerts a significant effect on RA, clinically manifested by damage of the joints. RA is significantly associated with periodontitis, which is caused by an increased abundance of Porphyromonas gingivalis in the subgingival niche, which disturbs the homeostasis of the oral microbial community. P. gingivalis is considered to contribute to the development and progression of RA. Although this bacterium may escape detection by the host immune system, it still induces an immune imbalance. RA and periodontitis also share similar pathological and clinical features. The progression of both chronic periodontitis and RA is linked to the dysregulation of the immune system and the damage caused by the immune response. Previous detailed studies have indicated that a specific enzyme of P. gingivalis, peptidyl-arginine deiminase, which catalyzes the citrullination of proteins, may trigger the autoimmune response resulting in the development of RA.

Is Periodontal and Peri- Implant Disease Associated with Fixed Partial Denture Use? A 25-year Prospective Case Series.

The association of the periodontium with the fixed prosthesis is the basis of prosthetic rehabilitation. This prospective case series aimed to evaluate periodontal health through the relation between periodontal/peri-implant disease progression and the use of fixed partial dentures (FPDs). Probing depth (PD), clinical attachment level (CAL), gingival index (GI), and plaque index (PI) on either teeth or implants were evaluated at up to 25-year follow-up and compared with the baseline. Statistical analysis was performed using the Kaplan-Meier test (p⟨0.05). The prospective evaluation showed that the patients maintained adequate periodontal health. Failure (severe periodontal stages) occurred in 12.5% of patients. The survival rate for 107 teeth/implants was 80.48%. The comparisons for clinical parameters revealed no statistically significant difference (p⟩ 0.05). At T1, the measurements for anterior and posterior regions, respectively, were PD =2.7mm and 3.1mm; CAL= 3.3mm and 3.6mm; GI=0.5 (both regions); and PI=0.79 and 0.62. Periodontal/peri-implant disease progression did not relate to the use of prostheses. Patients with more frequent follow-up appointments and lower GI and PI showed periodontal health for longer periods. Patients with different oral hygiene levels present different periodontal disease progression. Periodic hygiene control and motivation are vital factors for extensive oral rehabilitation success.

Tim4 deficiency reduces CD301b+ macrophage and aggravates periodontitis bone loss

Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth loss. With the progression of periodontitis, the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone resorption. CD301b+ macrophages are specific to the osteoimmunology microenvironment, and are emerging as vital booster for conducting bone regeneration. However, the key upstream targets of CD301b+ macrophages and their potential mechanism in periodontitis remain elusive. In this study, we concentrated on the role of Tim4, a latent upstream regulator of CD301b+ macrophages. We first demonstrated that the transcription level of Timd4 (gene name of Tim4) in CD301b+ macrophages was significantly upregulated compared to CD301b− macrophages via high-throughput RNA sequencing. Moreover, several Tim4-related functions such as apoptotic cell clearance, phagocytosis and engulfment were positively regulated by CD301b+ macrophages. The single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in macrophages. The following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b+ macrophages as periodontitis progressed. Furthermore, the deficiency of Tim4 in mice decreased CD301b+ macrophages and eventually magnified alveolar bone resorption in periodontitis. Additionally, Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b+ macrophages phenotype. In a word, Tim4 might regulate CD301b+ macrophages through p38 MAPK signaling pathway in periodontitis, which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.

Autoinducer-2 produced by oral microbial flora and alveolar bone loss in periodontitis.

The aim of this study was to investigate the association between autoinducer-2 (AI-2) of oral microbial flora and the alveolar bone destruction in periodontitis to determine if AI-2 may have the potential that monitor periodontitis and predict bone loss. Plaque biofilm was the initiating factor of periodontitis and the essential factor of periodontal tissue destruction. The formation of biofilms depended on the complex regulation of the quorum sensing (QS) system, in which bacteria could sense changes in surrounding bacterial density by secreting the autoinducer (AI) to regulate the corresponding physiological function. Most oral bacteria also communicated with each other to form biofilms administrating the QS system, which implied that the QS system of periodontal pathogens was related to periodontitis, but the specific relationship was unknown. We collected the gingival crevicular fluid (GCF) samples and measured the concentration of AI-2 in samples using the Vibrio harveyi BB180 bioluminescent-reporter system. To explore the interaction between AI-2 and bone metabolism, we utilized AI-2 purified from Fusobacterium nucleatum to investigate the impact of F. nucleatum AI-2 on osteoclast differentiation. Moreover, we constructed murine periodontitis models and multi-species biofilm models to study the association between AI-2 and periodontal disease progression. The AI-2 concentration in GCF samples increased along with periodontal disease progression (p < .0001). F. nucleatum AI-2 promoted osteoclast differentiation in a dose-dependent manner. In the periodontitis mice model, the CEJ-ABC distance in the F. nucleatum AI-2 treatment group was higher than that in the simple ligation group (p < .01), and the maxilla of the mice in the group exhibited significantly lower BMD and BV/TV values (p < .05). We demonstrated that the AI-2 concentration varied with the alveolar bone destruction in periodontitis, and it may have the potential for screening periodontitis. F. nucleatum AI-2 promoted osteoclast differentiation in a dose-dependent manner and aggravated bone loss.

STING inhibition alleviates bone resorption in apical periodontitis.

The goal of this study was to investigate the potential effects of an immunotherapeutic drug targeting STING to suppress the overreactive innate immune response and relieve the bone defect in apical periodontitis. We established an apical periodontitis mouse model in Sting-/- and WT mice in vivo. The progression of apical periodontitis was analysed by micro-CT analysis and H&E staining. The expression level and localization of STING in F4/80+ cells were identified by IHC and immunofluorescence staining. RANKL in periapical tissues was tested by IHC staining. TRAP staining was used to detect osteoclasts. To clarify the effect of STING inhibitor C-176 as an immunotherapeutic drug, mice with apical periodontitis were treated with C-176 and the bone loss was identified by H&E, TRAP, RANKL staining and micro-CT. Bone marrow-derived macrophages (BMMs) were isolated from Sting-/- and WT mice and induced to osteoclasts in a lipopolysaccharide (LPS)-induced inflammatory environment in vitro. Moreover, WT BMMs were treated with C-176 to determine the effect on osteoclast differentiation by TRAP staining. The expression levels of osteoclast-related genes were tested using qRT-PCR. Compared to WT mice, the bone resorption and inflammatory cell infiltration were reduced in exposed Sting-/- mice. In the exposed WT group, STING was activated mainly in F4/80+ macrophages. Histological staining revealed the less osteoclasts and lower expression of osteoclast-related factor RANKL in Sting-/- mice. The treatment of the STING inhibitor C-176 in an apical periodontitis mice model alleviated inflammation progression and bone loss, similar to the effect observed in Sting-/- mice. Expression of RANKL and osteoclast number in periapical tissues were also decreased after C-176 administration. In vitro, TRAP staining showed fewer positive cells and qRT-PCR reflected decreased expression of osteoclastic marker, Src and Acp5 were detected during osteoclastic differentiation in Sting-/- and C-176 treated BMMs. STING was activated and was proven to be a positive factor in bone loss and osteoclastogenesis in apical periodontitis. The STING inhibitor C-176 administration could alleviate the bone loss via modulating local immune response, which provided immunotherapy to the treatment of apical periodontitis.

Oral Lactobacillus zeae exacerbates the pathological manifestation of periodontitis in a mouse model.

The worldwide prevalence of periodontitis is considerably high, and its pathogenic mechanisms must be investigated and understood in order to improve clinical treatment outcomes and reduce the disease prevalence and burden. The exacerbation of the host immune system induced by oral microbial dysbiosis and the subsequent tissue destruction are the hallmarks of the periodontitis. However, the oral bacteria involved in periodontitis are not fully understood. We used the Oxford Nanopore Technologies (ONT) sequencing system to analyze metagenomic information in subgingival dental plaque from periodontitis and non-periodontitis patients. The number of Lactobacillus zeae (L. zeae) in the periodontitis patients was 17.55-fold higher than in the non-periodontitis patients, suggesting that L. zeae is a novel periodontitis-associated pathogen. Although several Lactobacillus species are used in vivo as probiotics to treat periodontitis and compete with Porphyromonas gingivalis (P. gingivalis), the roles of L. zeae in periodontitis progression, and the relationship between L. zeae and P. gingivalis needs to be investigated. Both L. zeae and P. gingivalis were inoculated in the ligature-implant site of periodontitis mice. We collected mouse gingival crevicular fluid to analyze inflammatory cytokine secretion using a multiplex assay. Intact or sliced mouse maxilla tissue was used for micro-computed tomography analysis or hematoxylin and eosin staining, immunohistochemistry, and tartrate-resistant acid phosphatase staining to evaluate alveolar bone loss, neutrophil infiltration, and osteoclast activation, respectively. We observed that L. zeae competed with P. gingivalis, and it increased inflammatory cytokine secretion at the ligature-implant site. Similar to P. gingivalis, L. zeae promoted ligature-induced neutrophile infiltration, osteoclast activation, and alveolar bone loss. We, therefore, concluded that L. zeae accelerated the progression of periodontitis in the ligature-induced periodontitis mouse model.

Exploring the In Vitro Antibacterial Potential of Specific Probiotic Strains against Oral Pathogens.

The microbiota in the oral cavity has a strict connection to its host. Its imbalance may determine oral diseases and can also have an impact on the systemic health. Probiotic strains may help in the restoration of a balanced condition. For this purpose, we screened the antibacterial and antiadhesive activities of many viable probiotic strains (Lactobacillus acidophilus PBS066, Lactobacillus crispatus LCR030, Lactobacillus gasseri LG050, Lactiplantibacillus plantarum PBS067, Limosilactobacillus reuteri PBS072, Lacticaseibacillus rhamnosus LRH020, Bifidobacterium animalis subsp. lactis BL050, Lacticaseibacillus paracasei LPC 1101, L. paracasei LPC 1082, and L. paracasei LPC 1114) against two main oral pathogens, Streptococcus mutans and Aggregatibacter actinomycetemcomitans, involved in dental caries and periodontal disease development and progression. Considering both the agar overlay preventive and treatment models, seven probiotics determined greater inhibition zones against the tested pathogens. This behavior was further analyzed by the plate count method and scanning electron microscope imaging. L. plantarum PBS067, L. rhamnosus LRH020, L. paracasei LPC 1101, L. paracasei LPC 1082, and L. paracasei LPC 1114 prevent the growth and adhesion of oral pathogens in a strain-specific manner (p < 0.0001). These probiotics might be considered as an alternative effective adjuvant to improve oral and systemic well-being for future personalized treatments.

Green Robusta Coffee Bean Extract (GRCBE) inhibits bone loss in wistar rat models of Lps P. gingivalis and NiTi wire-induced experimental periodontitis

Oral exposure to alloys frequently leads to negative reactions, both in the immediate area and across the body. The usage of coffee extracts is anticipated to enhance cellular function by counteracting the effects of pro-inflammatory signals that are involved in chronic inflammatory responses triggered by inflammatory agents like bacteria and metal ions. The objective is to develop a new approach using an extract obtained from Robusta coffee beans as an anti-inflammatory substance, which may have therapeutic benefits in preventing bone loss in Periodontitis Rat. The main cause is primarily attributed to the existence of metals and LPS P. gingivalis in the oral cavity. Methods. A randomized controlled trial was conducted, enroling 35 male Wistar rats that were divided into 7 groups and used as the experimental animals. Groups 1–4 consisted of rats that did not receive any therapy, while groups 5–7 comprised rats that were treated with GRCBE. The rats were subjected to decapitation after 14 days. The Green Robusta Coffee bean extract (GRCBE) was derived from the unprocessed green beans of Javanese Robusta coffee. We discovered in prior experimental experiments that GRCBE at a concentration of 500 mg/ml can inhibit the progression of periodontitis in rats. The substances used to cause inflammation and immune system impairment were NiTi wire and LPS P. gingivalis. Immunohistochemistry was used to assess the expressions of OCN, BMP2, and COX-2. Results. The simultaneous exposure of P. gingivalis lipopolysaccharide (LPS) and NiTi wire in rats led to an upregulation of OCN and BMP2 expression, while the expression of COX-2 reduced. The administration of GRCBE resulted in a steady drop in pro-inflammatory biomarkers, specifically OCN and BMP2, while the anti-inflammatory biomarker COX2 rose. In conclusion. In the field of dentistry, the coexistence of P. gingivalis LPS and metallic biomaterials can influence the occurrence of alveolar bone resorption in a rat model of periodontitis. GRCBE exhibits potential as an innovative approach for reducing periodontitis induced by the simultaneous activation of metal and LPS P. gingivalis. In this setting, it has the potential to be employed as an anti-inflammatory remedy.