Static magnetic field contributes to osteogenic differentiation of hPDLSCs through the H19/Wnt/ß-catenin axis.

BACKGROUND: Static magnetic field (SMF) as an effective physical stimulus is capable of osteogenic differentiation for multiple mesenchymal stem cells, including human periodontal ligament stem cells (hPDLSCs). However, the exact molecular mechanism is still unknown. Therefore, this study intends to excavate molecular mechanisms related to SMF in hPDLSCs using functional experiments. METHODS: hPDLSCs were treated with different intensities of SMF, H19 lentivirus, and Wnt/ß-catenin pathway inhibitor (XAV939). Changes in osteogenic markers (Runx2, Col Ⅰ, and BMP2), Wnt/ß-catenin markers (ß-catenin and GSK-3ß), and calcified nodules were examined using RT-qPCR, western blotting, and alizarin red staining in hPDLSCs. RESULTS: SMF upregulated the expression of H19, and SMF and overexpressing H19 facilitated the expression of osteogenic markers (Runx2, Col Ⅰ, and BMP2), activation of the Wnt/ß-catenin pathway, and mineralized sediment in hPDLSCs. Knockdown of H19 alleviated SMF function, and treatment with XAV939 limited SMF- and H19-mediated osteogenic differentiation of hPDLSCs. Notably, the expression of hsa-miR-532-3p, hsa-miR-370-3p, hsa-miR-18a-5p, and hsa-miR-483-3p in hPDLSCs was regulated by SMF, and may form an endogenous competitive RNA mechanism with H19 and ß-catenin. CONCLUSION: SMF contributes to the osteogenic differentiation of hPDLSCs by mediating the H19/Wnt/ß-catenin pathway, and hsa-miR-532-3p, hsa-miR-370-3p, hsa-miR-18a-5p, and hsa-miR-483-3p may be the key factors in it.

Periodontal disease: A systemic condition.

For decades, periodontitis has been considered to be a local inflammatory disease of the periodontal tissues in the oral cavity. Initially, associations of periodontitis with a multitude of noncommunicable diseases were each studied separately, and relationships were shown. The associations of periodontitis with morbidities, such as cardiovascular diseases, rheumatoid arthritis, diabetes mellitus, respiratory diseases, have been demonstrated. As most such studies were cross-sectional in nature, questions about causality cannot be univocally answered. And periodontitis as an independent risk factor for one systemic disease, becomes even more difficult to assess since recently periodontitis has also been associated with multimorbidity. Periodontitis and many systemic diseases share environmental, lifestyle and genetic risk factors, and share immunopathology. Moreover, suffering from one common noncommunicable disease may increase the susceptibility for another such chronic disease; the systemic effects of one condition may be one of various risk factors for another such disease. The overarching effect of any systemic disease is it causing a pro-inflammatory state in the individual; this has also been shown for periodontitis. Moreover, in periodontitis a prothrombotic state and elevated immunological activity have been shown. As such, when we consider periodontal disease as another systemic disease, it can affect the susceptibility and progression of other systemic diseases, and importantly, vice versa. And with this, it is not surprising that periodontitis is associated with a variety of other noncommunicable diseases. The medical definition of a systemic disease includes diseases that affect different organs and systems. Thus, the aim of this opinion paper is to propose that periodontitis should be considered a systemic disease in its own right and that it affects the individual's systemic condition and wellbeing. The dental and medical profession and researchers alike, should adapt this paradigm shift, advancing periodontal disease out of its isolated anatomical location into the total of chronic noncommunicable diseases, being for some conditions a comorbid disease and, vice versa, comorbidities can affect initiation and progression of periodontal disease.

Assessment Tools for Masticatory Function in Periodontitis Patients: A Scoping Review.

AIMS: The aim of this scoping review was to map the available evidence on assessment tools for masticatory function for periodontitis patients. It also aimed to examine the methodology of masticatory function assessment and to identify the elements of subjective masticatory function evaluation for periodontitis patients reported in the literature. METHODS: A scoping review was conducted following the methodological guidance for the conduct of scoping reviews. Embase, MEDLINE, Web of Science, and Scopus were systematically searched for published studies in English reporting objective or subjective masticatory function assessment in periodontitis patients. RESULTS: Forty-five studies were included in the analysis. The identified assessment tools for masticatory function were summarized using the terminology described by the recent consensus. Heterogeneity was observed in the approach of assessment, the type(s) and design of assessment tools, and the methods of measurement employed. Most studies utilized only one assessment tool. Seven studies reported composite objective assessment and five studies utilized assessment tools for both objective and subjective masticatory function. Items from the included instruments for subjective masticatory function were analyzed and categorized into seven potentially clinically relevant elements of subjective masticatory function evaluation. Unclear reporting on validation status was found in all included instruments for subjective masticatory function. CONCLUSION: Variable methodologies have been reported to assess masticatory function in periodontitis patients. Future research is needed to discern the clinical utility of these assessment tools for masticatory function in periodontitis patients.

Appraising the life-course impact of Epstein-Barr virus exposure and its genetic signature on periodontitis.

BACKGROUND: Periodontitis arises from a multifaceted interplay of environmental variables and genetic susceptibility, where microbial infection plays an indispensable part. Epstein-Barr virus (EBV) exposure has long been considered associated with periodontitis activity; however, the causal relationship and genetic connection between them remain unknown. METHODS: Within a life-course context, our study employed comprehensive Mendelian randomization (MR) methods, including univariable, multivariable, Bayesian model averaging, and reverse MR, to investigate the causal association between EBV exposure and periodontitis. Additionally, linkage disequilibrium score regression and colocalization analysis were utilized to assess the cross-trait genetic correlations, followed by transcriptome-wide association and enrichment analysis to discern the genetic-phenotypic biological profiles. RESULTS: Heightened levels of EBV antibodies, particularly early antigen diffuses (which serve as indicators of early infection or reactivation), are associated with an increased risk of periodontitis (odds ratio [OR]: 1.27 [1.09-1.47], p = 6.05 × 10-3) and demonstrate a significant genetic correlation (p = 4.11 × 10-3). This pathogenesis may involve the high-confidence causal gene RNASEK located in 17p13.1. Genetically predicted early-life anti-EBV immunoglobulin G (IgG) levels are correlated to a reduced periodontitis risk (OR: 0.89 [0.82-0.97], p = 1.76 × 10-3). CONCLUSIONS: The present study highlights the impact of life-course EBV exposure and its genetic hallmark on periodontitis, providing novel perspectives into the underlying pathogenesis and management strategies for EBV-related periodontitis. These findings underscore diverse clinical and public health implications, encompassing antiviral therapies, viral vaccination strategies, and tailored interventions for individualized periodontitis management. Further research is required to validate and expand upon our findings. PLAIN LANGUAGE SUMMARY: Periodontitis is a chronic inflammatory disease driven by interactions between microbial pathogens and the host immune system. While bacteria have traditionally been the focus of research, recent studies highlight the significance of virus-bacteria interactions, particularly the role of Epstein-Barr virus (EBV)-a herpesvirus infecting over 90% of the global population-in the development of periodontitis. However, the underlying causal and genetic mechanisms remain unclear. Our study employed genome-wide multi-omics approaches to investigate the link between EBV exposure and periodontitis. We found that recent EBV infection or reactivation increases the risk of periodontitis, whereas early-life exposure, possibly enabling immune resistance, may reduce it. Essential genes were identified as potential mediators, including CRTC3-AS1, HLA-DQA1, and RNASEK. These findings provide novel insights into the EBV-periodontitis connection. For example, viral testing and control could benefit patients unresponsive to standard bacterial treatments, and early viral exposure via vaccination might reduce the risk of periodontitis. Further clinical studies are required to elucidate these underlying mechanisms and the contribution of virus-bacteria interactions.

The association of reproductive health factors with periodontitis in 45-80 years old US women from NHANES 2009-2014.

OBJECTIVES: We investigated the association of female reproductive factors with periodontitis. MATERIALS AND METHODS: This cross-sectional study analyzed data from the US National Health and Nutrition Examination Survey 2009-2014 on 2321 women aged 45-80 years who had full-mouth periodontal examination and reproductive questionnaire. The 2018 World Workshop Classification of Periodontal and Peri-implant Diseases was used to classify periodontitis stages. RESULTS: After adjustment, > 3 pregnancies or live births were associated with increased stage III/IV periodontitis but age at first birth (AFB) > 23 years and female hormone use were associated with decreased stage III/IV periodontitis, while there were no associations of oral contraceptive use or menopause status with stage III/IV periodontitis. Stage III/IV periodontitis was more common in women with > 3 pregnancies or live births and AFB ≤ 23 years or never using female hormones but less common in women with ≥ 3 pregnancies or > 3 live births and AFB > 23 years or using female hormones. >3 pregnancies or live births were related with increased stage III/IV periodontitis and increased AFB was related with lowered stage III/IV periodontitis in overweight and smoking subgroups but using female hormone was related with reduced stage III/IV periodontitis in nonsmoking, non-overweight and black subgroups. CONCLUSIONS: >3 pregnancies/live births were related with severe periodontitis but AFB > 23 years and female hormone use were related with ameliorating periodontitis. CLINICAL RELEVANCE: Women with > 3 pregnancies/live births should receive intensive periodontal interventions. Female hormone therapy or AFB > 23 years may be beneficial for periodontal health of > 3 pregnancies/live births women.

Preparation and Evaluation of Poloxamer/Carbopol In-Situ Gel Loaded with Quercetin: In-Vitro Drug Release and Cell Viability Study.

BACKGROUND: Periodontitis is a severe chronic inflammatory disease, whose traditional systemic antimicrobial therapy faces great limitations. In-situ gels provide an effective solution as an emerging local drug delivery system. METHODS: In this study, the novel thermosensitive poloxamer/carbopol in-situ gels loaded with 20 µmol/L quercetin for the treatment of periodontitis were prepared by cold method. Thirteen batches of in-situ gels based on two independent factors (X1: poloxamer 407 and X2: carbopol 934P) were designed and optimized by the statistical method of central composite design (CCD). The transparency, pH, injectability, viscosity, gelation temperature, gelation time, elasticity modulus, degradation rate and in-vitro drug release studies of the batches were evaluated, and the percentage of drug release in the first hour, the time required for 90% drug release, gelation temperature, and gelation time were selected as dependent variables. RESULTS: These two independent factors significantly affected the four dependent variables (p < 0.05). The optimization result displayed that the optimized concentration of poloxamer 407 was 20.84% (w/v), and carbopol 934P was 0.5% (w/v). The optimized formulation showed a clear appearance (++), acceptable injectability (Pass), viscosity(151,798 mPa s), gelation temperature (36 °C), gelation time (213 s), preferable cell viability and cell proliferation, conformed to first-order release kinetics, and had a significant antibacterial effect. CONCLUSIONS: The article demonstrates the great potential of the quercetin in-situ gel as an effective treatment for periodontitis.

Allyl isothiocyanate suppressed periodontal tissue destruction in mice via bacteriostatic and anti-inflammatory activities against Porphyromonas gingivalis.

OBJECTIVES: Allyl isothiocyanate (AITC) is a phytochemical that is abundantly present in cruciferous vegetables, such as wasabi and mustard. Among its pharmacological properties, it demonstrates anticancer, antifungal, and anti-inflammatory activities. This study aimed to investigate the functions of AITC against periodontopathic bacteria and its effects on a mouse model of periodontitis. DESIGN: The antimicrobial and antibiofilm functions of AITC were assessed against Porphyromonas gingivalis, Fusobacterium nucleatum, and Streptococcus mitis. To clarify its anti-inflammatory effects, macrophage-like cells from THP-1 were stimulated with P. gingivalis lipopolysaccharide (LPS), and the release of inflammatory cytokines was analyzed by ELISA. Experimental periodontitis was induced in 9-week-old mice by ligation and oral infection of P. gingivalis, and AITC was injected into the gingiva once daily for 8 days. Alveolar bone resorption was evaluated by measuring the exposed root area. Gene expressions in the periodontal tissue were analyzed via qPCR. RESULTS: AITC exerted weak bacteriostatic effects against P. gingivalis, inhibiting biofilm formation. AITC also impeded the production of interleukin-6 and tumor necrosis factor-α induced by P. gingivalis LPS. Additionally, transient receptor potential ankyrin 1(TRPA1) channel agonist inhibited the anti-inflammatory effects of AITC. In vivo, AITC inhibited alveolar bone destruction and decreased the gene transcription of Il6 in the periodontal tissue. CONCLUSION: AITC exerted weak bacteriostatic and anti-inflammatory effects against P. gingivalis, reducing alveolar bone destruction and suppressing the inflammatory response in experimental periodontitis. Therefore, AITC may serve as a valuable adjunct in controlling periodontal disease.

Non-Surgical Endodontic Management of Large Periapical Lesions After Traumatic Dental Injuries.

Traumatic dental injuries of permanent teeth result in multiple immediate and long-term consequences depending upon the severity of trauma, age of the patient, the status of root maturity, and the emergency care provided. The healing responses may get disturbed due to severe damage, loss of vascularity of the supporting structures, and infections. As a result, the prohealing mediators and pathways are overpowered by the destructive stimuli often manifested by an increased osteoclastic activity. Among the various late complications, the apical periodontitis or the periapical lesions are most worrisome for the patients and create clinical dilemma for the dentists. In the past, many such lesions were classified as cysts and subjected to surgical management. However, better understanding of lesion pathophysiology, three-dimensional imaging, and molecular pathways have established their inflammatory nature. The advancements in materials such as calcium silicates, and regenerative techniques have propelled the research related to non-surgical endodontic management as its clinical acceptability. The treatment largely follows the recommendations of regenerative medicine and is based on four principles: (a) establishing the drainage or an endodontic access to the area, (b) removal of most of the triggering agents such as necrosed pulp, toxins, and inflammatory mediators, (c) disinfection of the area, controlling inflammation and reversal of the acidic pH, and (d) maintenance of this infection/inflammation-free state for a long time through adequate sealing. This review aims to highlight the rationale of the approach, case selection, pathophysiology of the causation and healing, clinical protocols, and the limitations of non-surgical endodontic management of large periapical lesions secondary to traumatic dental injuries.

Alterations in subgingival microbiome and advanced glycation end-products levels in periodontitis with and without type 1 diabetes mellitus: a cross-sectional study.

BACKGROUND: Existing studies predominantly focused on the relationship between periodontitis and type 2 diabetes mellitus (T2DM), with limited data on the association between periodontitis and type 1 diabetes mellitus (T1DM). This study aimed to examine the impact of T1DM and periodontitis on the subgingival microbiome and levels of advanced glycation end-products (AGEs). METHODS: Samples were collected from four groups: T1DM, periodontitis (P), T1DM with periodontitis (DP), and periodontally and systemically healthy controls (Control). Subgingival microbiome composition and AGE levels were assessed using 16S rRNA gene sequencing and enzyme-linked immunosorbent assay (ELISA), respectively. Correlations between clinical indexes, microbiome composition, and AGEs were analyzed using Spearman correlation coefficient. RESULTS: Alpha and beta diversity analyses revealed significant differences in bacterial diversity between the DP group and other groups. Linear discriminant analysis effect size (LEfSe) analysis identified specific bacteria influencing each group: Acinetobacter, Leptotrichia, Raoultibacter, and Veillonella in the Control group; Tannerella, Porphyromonas, Filifactor, and Treponema in the P group; and Lactobacillales in T1DM individuals. Prevotella and Selenomonas were notably influential in the DP group. PICRUSt2 analysis showed pathways alterations were concentrated in cell motility, translation, cell growth and death and metabolism in the DP and P groups. Spearman correlation analysis indicated a positive correlation between AGEs and periodontitis or diabetes-related parameters and AGEs were positively correlated with Haemophilus and Arachnia. CONCLUSIONS: The findings suggested that the composition and function of the subgingival microbiome in the P group with or without T1DM were significantly different. Additionally, AGEs were involved in the development of periodontitis even in absence of hyperglycemia.

Bilateral parapneumonic empyema caused by Fusobacterium necrophorum infection in a healthy individual.

Pulmonary infection caused by Fusobacterium necrophorum, an obligate anaerobic gram-negative bacterium, most commonly occurs as a part of Lemierre's syndrome, i.e., pharyngotonsillitis complicated by septic thrombophlebitis of the internal jugular vein and secondary lung abscesses. A 51-year-old previously healthy man was admitted to our hospital with pleuritic right-sided chest pain. No sore throat, dysphagia, or neck pain was observed. Chest radiography and computed tomography (CT) revealed massive right pleural effusion and bilateral bronchopneumonia. Right thoracic drainage yielded purulent fluids, from which a pure culture of F. necrophorum was isolated. Blood culture and broad-range polymerase chain reaction for bacterial 16S ribosomal ribonucleic acid on blood samples were negative. CT scan showed no evidence of internal jugular vein thrombosis or peritonsillar abscess. The right thoracic tube was removed after the purulent fluids were no longer drained. Although the antibiotic treatment was continued with intravenous sulbactam/ampicillin, to which F. necrophorum was sensitive, left purulent pleural effusion emerged. The antibiotic was switched to clindamycin, cefazolin, cefotiam, and flomoxef. Although the left pleural effusion gradually decreased, the right purulent pleural fluid was reaccumulated. Thus, the patient underwent right-sided thoracoscopic decortication and debridement, followed by thoracic lavage through a chest tube with saline solution. After the surgery, the patient's condition improved, and no recurrence of pleural effusion was observed. This report presents the case of a previously healthy patient with bilateral parapneumonic empyema caused by F. necrophorum, without manifestations of pharyngotonsillitis, bacteremia, or Lemierre's syndrome. Extensive thoracic drainage, effective antibiotics, and timely surgical interventions are imperative.

Procyanidin B2 targeted CCR7 expression to inhibit the senescence-associated secretory phenotype through the NF-κB pathway to promote osteogenic differentiation of periodontal ligament stem cells in periodontitis.

Periodontitis is recognized as a chronic inflammatory disease, with aging emerging as a significant risk factor. Cellular senescence plays a crucial role in the biological process of aging. The senescence-associated secretory phenotype (SASP) is characterized by a series of pro-inflammatory factors, chemokines, and proteases, which are hallmark characteristics of senescent cells. These factors collectively alter the local environment, impacting the function of periodontal ligament stem cells (PDLSCs). Procyanidin B2 (PB2), the main dimer of oligomeric procyanidins, possesses antioxidant, anti-inflammatory, and anti-cancer properties. The molecular mechanisms through which PB2 exerts its protective effects against periodontitis remain incompletely understood. Therefore, this research aimed to investigate the effects and underlying mechanisms of PB2 on the osteogenic differentiation of PDLSCs within an inflammatory environment. To simulate a chronic inflammatory condition, PDLSCs were stimulated with Porphyromonas gingivalis Lipopolysaccharide (Pg. LPS). The findings indicated that PB2 significantly alleviated the inflammatory responses, enhanced the activity of antioxidant enzymes, and upregulated the osteogenic differentiation of PDLSCs stimulated by Pg. LPS. RNA sequencing (RNA-Seq) revealed that Pg. LPS influenced the cell cycle, cellular senescence, and NF-κB signaling pathways. In contrast, PB2 treatment reduced the number of senescent cells and diminished the expression of senescence-associated proteins and genes. Western blot analysis verified that PB2 also decreased the levels of CCR7 and suppressed the NF-κB signaling pathways. In conclusion, PB2 targeted CCR7 expression to inhibit the SASP through NF-κB signaling pathway, demonstrating its anti-inflammatory and osteogenic properties, positioning PB2 as a promising therapeutic option for the adjuvant treatment of periodontitis.

Iodine deficiency and its association with periodontitis: A randomized controlled triple-blinded clinical study.

BACKGROUND: Numerous research studies have explored the impact of micronutrients, including dietary minerals such as iron, zinc, selenium, copper, and vitamins A, B complex, C, D, and E, on periodontitis. However, there is no literature investigating the role of iodine in periodontal health. OBJECTIVES: This study aimed to examine the potential influence of iodine, a trace element, on periodontal health, an area that has not yet been researched. MATERIAL AND METHODS: The study recruited a total of 73 participants, including 33 periodontally healthy control subjects and 40 patients with stage III periodontitis. Iodine levels in urine samples were measured using a spectrophotometric method, and the results were expressed in µg/L. RESULTS: Lower iodine levels were observed in patients with periodontitis. Individuals with low iodine levels were found to be 1.04 times more likely to develop periodontitis than those with high iodine levels. The study found that if a person's urine iodine value is below 76.93 µg/L, the probability of having periodontitis is 72.5%; if it is above this value, the probability of not having periodontitis is 90.9%. CONCLUSIONS: These findings suggest that urinary iodine levels could be a valuable metric for future research, as indicated by the variance in mean urinary iodide levels. Further extensive studies could establish urinary iodine levels as a useful biomarker for the diagnosis, prognosis and treatment plan of periodontitis.

Hormone Replacement Therapy Relieves Periodontitis by Inhibiting Alveolar Bone Loss and Inflammation.

OBJECTIVE: Hormone replacement therapy (HRT) is a commonly used strategy for treating menopausal symptoms, while its relation with periodontitis remains unclear. This study aimed to explore the potential effects of HRT on periodontitis, mainly in aspects of bone loss and inflammation. METHODS: The alveolar bone height (ABH), alveolar bone thickness (ABT), and bone mineral density (BMD) were measured in menopausal women with periodontitis who had received HRT or had not received HRT by cone beam computed tomography. Based on a rat model of periodontitis, the alveolar bone loss was evaluated by micro-computed tomography and bone-related biochemical markers. The expression/levels of inflammatory markers were measured to reflect periodontal inflammation. RESULTS: Although the differences were not all significant in each premolars/molars, the mesial/distal ABH and buccal/lingual ABT were lower, and the mesial/distal BMD was higher in patients in the HRT group than those in the control group. In a rat model of periodontitis, the alveolar bone loss was relieved by HRT. Additionally, HRT significantly weakened the elevation of inflammatory markers, including TNF-α, IL-1ß, and IL-6 in periodontitis rats. CONCLUSIONS: HRT contributes to the remission of periodontitis by inhibiting alveolar bone loss and inflammation.

TNF-alpha gene promoter's hypomethylation mediates a pro-inflammatory phenotype in peripheral blood monocytes from apical periodontitis individuals.

AIM: Epigenetic regulation of the key inflammatory genes plays a crucial role in controlling monocyte/macrophage-mediated local and systemic responses to bacterial challenges. However, it has not been addressed in apical periodontitis (AP). We aimed to explore the methylation pattern of the TNF-α gene promoter and its association with the inflammatory phenotype of peripheral blood monocytes from individuals with AP and controls. METHODS: A cross-sectional study was conducted, including otherwise healthy individuals with AP (n = 25) and controls (n = 29). Monocytes were isolated from the volunteer's blood samples using a Ficoll gradient followed by negative immunoselection. RNA and DNA were extracted. The DNA methylation profiles of the TNF-α gene promoter region were analyzed using bisulfite sequencing PCR. The mRNA expression levels of DNA methyltransferases 3a (DNMT3a) and Ten Eleven Translocation enzymes 1(TET1) were assessed by qPCR. A fraction of primary monocytes was also cultured for 24 h, and the supernatant was collected to measure cytokine levels through a Luminex assay. Generalized structural equation models (GSEM) evaluated the association between AP, DNA methylation, and TNF-α protein expression controlled for potential covariates. Models included the effect of the methylation of TNF-α gene promoter as a mediator of the association between AP and TNF-α protein expression levels. RESULTS: Monocytes from AP individuals exhibited a heightened secretion of TNF-α and IL-1ß and hypomethylation of the TNF gene promoter (p < .05). AP diagnosis was associated with the TNF-α gene promoter´s hypomethylated profile and enhanced pro-inflammatory cytokine levels, while lower methylation of the gene promoter region and -163 CpG single site mediated TNF-α overexpression (p < .05). CONCLUSIONS: DNA hypomethylation at the TNF-α gene mediates a proinflammatory phenotype in monocytes from AP patients, supporting a role in the systemic response.

Endodontic and periapical status of patients with osteoporosis: A cross-sectional study with age- and sex-matched controls.

BACKGROUND: The aim of the authors was to evaluate the periapical and endodontic conditions of patients with osteoporosis and compare them with those of age- and sex-matched controls. The association between bisphosphonate (BiP) use and periapical and endodontic status in patients with osteoporosis was also investigated. METHODS: Panoramic radiographs of 711 patients with osteoporosis and 711 age- and sex-matched healthy patients were examined. The presence and number of root canal-filled teeth (RCFT), inadequate RCFT (iRCFT), and teeth with apical periodontitis (AP) were evaluated. BiP treatment history of patients with osteoporosis was also recorded. RESULTS: No significant difference was observed between the osteoporosis group and control group in terms of endodontic and periapical conditions. Results of bivariate logistic regression analysis showed a positive association between the number of teeth with AP and the number of iRCFT with AP and osteoporosis, and a negative association between the number of RCFT with AP and osteoporosis. Among the patients with osteoporosis, 37.5% used BiPs, specifically alendronate, ibandronate, zoledronate, and risedronate (34.3%, 24.9%, 10.6%, 7.2%, respectively). In addition, the results showed a negative association between BiP use and RCFT. CONCLUSIONS: As the number of teeth with AP and number of iRCFT with AP increased, patients were more likely to be in the osteoporosis group. These findings imply that periapical lesions may enlarge and become more detectable in patients with osteoporosis with lower bone density, and enhanced inflammatory response. PRACTICAL IMPLICATIONS: Dentists can collaborate with health care professionals to manage the overall health of patients with osteoporosis to reduce the impact of osteoporosis on oral health and effectively treat dental problems, such as AP.

Periodontitis Is Associated With Arterial Stiffness as Measured by Serial Cardio-Ankle Vascular Index (CAVI): A 10-Year Cohort Study.

AIM: To investigate the effect of periodontitis on the long-term changes of the cardio-ankle vascular index (CAVI). MATERIALS AND METHODS: A 10-year retrospective cohort study of 3842 Thai participants (range 25-76 years) with normal CAVI at the study initiation was undertaken. Full-mouth periodontal examination was performed by calibrated periodontists, and the extent and severity of periodontitis were determined at 5-year intervals. Serial CAVI measurements were used to examine the incidence of high CAVI (≥ 9.0) and changes in CAVI over time (ΔCAVI). RESULTS: Participants with a higher extent or severity of periodontitis were found to have a significantly higher mean ΔCAVI. The incidence of high CAVI was also observed to be higher in those with periodontitis compared to those without it. The adjusted risk ratios for developing high CAVI were 1.309 and 1.513 for localized and generalized periodontitis, respectively. Participants with severe periodontitis had a 37% higher likelihood of developing CAVI ≥ 9.0 compared to individuals with no/mild periodontitis. This risk was consistent with a significant change in ΔCAVI of 0.054-0.140. CONCLUSIONS: Periodontitis, both in terms of extent and severity, was found to have a significant dose-dependent effect on the risk of developing high CAVI over a 10-year period, suggesting a causal relationship between these two parameters.

Chairside live biotherapeutic hydrogel for comprehensive periodontitis therapy.

Periodontitis, characterized by microbial dysbiosis and immune dysregulation, destroys tooth-supporting tissues and negatively affects overall health. Current strategies face significant challenges in restoring damaged tissues while halting periodontitis progression. In this study, we introduce a live biotherapeutic product (LBP) in an engineered living hydrogel for comprehensive periodontitis therapy. A dental blue light-responsive hydrogel (LRG) was fabricated to deliver and confine live Lactobacillus rhamnosus GG (LGG) in periodontal pockets, endowing the LRG with sustained antibacterial and immunomodulatory effects. The LRG was engineered through peptide modification to also promote tissue regeneration. Both in vitro and in vivo evaluations confirmed the effectiveness of this integrated therapeutic strategy, which combines antibacterial, anti-inflammatory, and regenerative properties with an underlying immunomodulatory mechanism that involves suppressor of cytokine signaling (SOCS)3 upregulation and the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway suppression in macrophages. Demonstrating a new paradigm, this proof of concept highlights the synergistic integration of live organisms and synthetic material engineering in a chairside treatment to address the multifaceted etiology of periodontitis.

Neutrophils suppress osteogenic differentiation of Gli1+ stem cells via neutrophil extracellular traps and contribute to bone loss in periodontitis.

Periodontitis is a severe and chronic oral inflammatory disease that leads to the progressive and irreversible destruction of periodontal tissues, ultimately resulting in tooth loss. Among the immune cell subtypes involved, neutrophils play a crucial role in the initiation and progression of periodontitis. Mesenchymal stem cells (MSCs) are essential components of periodontal tissue, contributing to tissue development, homeostasis, and regeneration. Recent studies have demonstrated that neutrophils significantly affect the function of MSCs by changing the inflammatory environment. However, the specific effects of neutrophils on periodontal MSCs during periodontitis remain unclear, highlighting a gap in our understanding of the disease mechanisms. In this study, we utilized the Gli1-CreERT2;mT/mG transgenic mouse model to specifically mark Gli1+ cells, a critical and representative subset of MSCs in the periodontal tissues responsible for maintaining tissue homeostasis. We reveal that neutrophils inhibit the osteogenic differentiation of Gli1+ cells and exacerbate alveolar bone destruction by secreting neutrophil extracellular traps (NETs), which induce endoplasmic reticulum stress in Gli1+ cells. These findings highlight the pivotal impact of neutrophils on distinct subpopulations of periodontal MSCs in the pathogenesis of periodontitis, offering valuable insights into the underlying mechanisms of the disease and suggesting potential future therapeutic strategies aimed at modulating the interactions between neutrophils and MSCs.

Benzylurea Protects hPDLFs Against LPS-Induced Mitochondrial Dysfunction Through MTCH2.

OBJECTIVE: The aim of this study is to explore the mechanism of benzylurea in the inflammatory injury of human periodontal ligament fibroblasts (hPDLFs). METHODS: An inflammation model of hPDLFs was established using LPS. Nuclear transport of nuclear transcription factor-κB (NF-κB), secretion of cytokines, and the morphology and distribution of F-actin were determined. Mitochondrial function was assessed by measuring mitochondrial membrane potential (MMP), mitochondrial permeability transition pore (mPTP), and reactive oxygen species (ROS) levels. The expression of mitochondrial carrier homolog 2 (MTCH2) and Cytochrome b5 type B (CYB5B) was detected. RESULTS: Benzylurea alleviated the effects of lipopolysaccharide (LPS) on the proliferation and apoptosis of hPDLFs. It reduced the release of inflammatory cytokines and inhibited NF-κB nuclear translocation. Benzylurea improved mitochondrial function by regulating MMP and preventing excessive mPTP opening. Furthermore, LPS elevated the expression of MTCH2 and reduced the expression of CYB5B in hPDLFs. However, these effects can be inhibited by benzylurea. The altered expression of MTCH2 directly affected CYB5B expression, the release of inflammatory cytokines, and the activation of nuclear translocation of NF-κB. CONCLUSION: CYB5B may act as an effector of MTCH2, with benzylurea enhancing mitochondrial function and protecting hPDLFs from LPS-induced injury through MTCH2.

Hypoxic Responses in Periodontal Tissues: Influence of Smoking and Periodontitis.

AIM: This study aimed to investigate the hypoxic changes in periodontal tissues resulting from smoking and periodontitis by assessing levels of hypoxia-inducible factors (HIF-1α, HIF-2α, HIF-3α) and vascular endothelial growth factor (VEGF) in gingival crevicular fluid (GCF). MATERIALS AND METHODS: The study comprised 22 periodontally healthy non-smokers (Group H), 22 periodontally healthy smokers (Group HS), 22 non-smokers with periodontitis (Group P) and 22 smokers with periodontitis (Group PS). Clinical periodontal parameters were documented, and GCF samples were collected and analysed using enzyme-linked immunosorbent assay (ELISA). RESULTS: Significantly elevated levels of HIF-1α, HIF-3α and VEGF were observed in Groups HS, P and PS compared to Group H (p < 0.05). Moreover, higher HIF-2α levels were detected in the Groups HS and P compared to Group H (p < 0.05). Significant correlations were detected between all evaluated hypoxia biomarkers in the Group P (p < 0.05) except HIF-2α and HIF-3α. However, in the PS group, significant correlation appeared only between HIF-1α and HIF-2α (p < 0.05). CONCLUSION: Our findings indicate that smoking and periodontitis induce comparable hypoxic effects in periodontal tissues, as evidenced by the evaluated biomarkers. Further research is warranted to gain a deeper understanding of the mechanisms underlying hypoxia in periodontal tissues.