RESUMEN

BACKGROUND: Activation of the IL-33/ST2 axis leads to the production of proinflammatory cytokines and thus to the triggering of osteoclastogenesis, which is why it plays an important role in the immunopathogenesis of periodontitis. The aim of this study was to compare IL-33 levels in serum, plasma, saliva and gingival crevicular fluid (GCF) of subjects with chronic periodontitis (CP) in comparison with the control group (CG). METHODS: This systematic review and meta-analysis followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and was registered in the Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/YHUWA . Six electronic databases were used for study identification; PubMed, Google Scholar, ScienceDirect, Web of Science, Scopus and Dentistry & Oral Sciences Source from March 10, 2012 to April 30, 2024. The Joanna Briggs Institute (JBI) tool was used to assess the quality of the included cross-sectional articles and clinical trials. RESULTS: Of the 949 articles identified, 14 were included according to the inclusion and exclusion criteria. The total number of individuals studied in the included investigations was 814 of whom 445 had CP and 369 were healthy. The reported age range was from 20 to 50 years, with a mean age ± standard deviation of 40.29 ± 7.83 years. Four hundred and twenty-six (52%) patients were men and 388 (48%) were women. Meta-analysis revealed that there is an increase in IL-33 levels in plasma, saliva and GCF of subjects with CP compared to CG (p = * < 0.05). CONCLUSIONS: This study found a significant increase in IL-33 levels in different biological samples (plasma, saliva and GCF) of individuals with CP compared to CG, thus IL-33 has potential to be a biomarker in the diagnosis of periodontitis.

Asunto(s)

Interleucina-33 , Humanos , Interleucina-33/sangre , Interleucina-33/metabolismo , Líquido del Surco Gingival/metabolismo , Periodontitis/metabolismo , Periodontitis/sangre , Periodontitis Crónica/metabolismo , Periodontitis Crónica/sangre , Biomarcadores/sangre , Biomarcadores/metabolismo , Saliva/metabolismo

RESUMEN

The objective of this study is to investigate the effects of a moderate intensity physical training protocol, on alveolar bone morphology of rats submitted to ligature-induced periodontitis. Twenty-eight male Wistar rats were divided into four groups, considering the presence/absence of periodontitis and presence/absence of training. The training protocol was performed on a treadmill, 30 min/day, 5 days a week, for 4 weeks. In the experimental periodontal breakdown, with/without training, ligatures were placed on the lower first molars on the 14th day of the experiment, and were followed until the end of the protocol. At the end of the experiment, animals were euthanized and samples of plasma and mandibles were collected for immunoenzymatic evaluation of interleukins (IL)-1ß, IL-6, TNF-α and IL-10, evaluation of serum concentrations of C-reactive protein, analysis of lipid peroxidation (LPO) and reduced glutathione, histological and microtomographic analyses were performed. Physical training resulted in a reduced levels of IL-1ß, IL-6, TNF-α C-reactive protein and LPO and an increase in the levels of IL-10 in rats with periodontitis (p<0.05); a reduction in the inflammatory infiltrate and decreased fiber degradation was identified in histological analysis. Additionally, it was shown a decrease in vertical bone loss and an increase in the bone volume/trabecular volume ratio was identified in periodontitis+physical training group (p<0.05). Based on the results, the practice of frequent physical exercise, at moderate intensity, can contribute to the reduction of damage related to the disproportionate inflammatory response in periodontitis.

Asunto(s)

Peroxidación de Lípido , Estrés Oxidativo , Periodontitis , Condicionamiento Físico Animal , Ratas Wistar , Animales , Periodontitis/metabolismo , Periodontitis/patología , Masculino , Ratas , Proteína C-Reactiva/metabolismo , Pérdida de Hueso Alveolar/patología , Pérdida de Hueso Alveolar/metabolismo , Glutatión/metabolismo , Modelos Animales de Enfermedad , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Citocinas/metabolismo , Citocinas/sangre

RESUMEN

Ferroptosis is implicated in the pathogenesis of numerous chronic-inflammatory diseases, yet its association with progressive periodontitis remains unexplored. To investigate the involvement and significance of ferroptosis in periodontitis progression, we assessed sixteen periodontitis-diagnosed patients. Disease progression was clinically monitored over twelve weeks via weekly clinical evaluations and gingival crevicular fluid (GCF) collection was performed for further analyses. Clinical metrics, proteomic data, in silico methods, and bioinformatics tools were combined to identify protein profiles linked to periodontitis progression and to explore their potential connection with ferroptosis. Subsequent western blot analyses validated key findings. Finally, a single-cell RNA sequencing (scRNA-seq) dataset (GSE164241) for gingival tissues was analyzed to elucidate cellular dynamics during periodontitis progression. Periodontitis progression was identified as occurring at a faster rate than traditionally thought. GCF samples from progressing and non-progressing periodontal sites showed quantitative and qualitatively distinct proteomic profiles. In addition, specific biological processes and molecular functions during progressive periodontitis were revealed and a set of hub proteins, including SNCA, CA1, HBB, SLC4A1, and ANK1 was strongly associated with the clinical progression status of periodontitis. Moreover, we found specific proteins - drivers or suppressors - associated with ferroptosis (SNCA, FTH1, HSPB1, CD44, and GCLC), revealing the co-occurrence of this specific type of regulated cell death during the clinical progression of periodontitis. Additionally, the integration of quantitative proteomic data with scRNA-seq analysis suggested the susceptibility of fibroblasts to ferroptosis. Our analyses reveal proteins and processes linked to ferroptosis for the first time in periodontal patients, which offer new insights into the molecular mechanisms of progressive periodontal disease. These findings may lead to novel diagnostic and therapeutic strategies.

Asunto(s)

Progresión de la Enfermedad , Ferroptosis , Líquido del Surco Gingival , Periodontitis , Humanos , Líquido del Surco Gingival/química , Periodontitis/metabolismo , Periodontitis/patología , Femenino , Masculino , Proteómica , Muerte Celular , Adulto , Persona de Mediana Edad , Western Blotting

RESUMEN

The aim of this study was to evaluate the effect of non-surgical periodontal treatment in the expression of chemokine receptors, in individuals with Periodontitis, associated or not with Diabetes. Pilot study, which included patients (n = 45) with Periodontitis, associated (n = 25) or not (n = 20) with Diabetes, submitted to the non-surgical periodontal treatment for one month. The expression of chemokine receptors CCR2, CCR5, and CX3CR1 at the mRNA level was evaluated in the peripheral mononuclear cells, as well as the expression of these receptors at the protein level was verified in monocyte subtypes (classical, intermediate, and non-classical monocytes). There was higher expression of CCR2 and CCR5 receptors at the initial visit in the group with Diabetes, with no differences for CX3CR1 (p = 0.002; p = 0.018, and p = 0.896, respectively), without differences after treatment. There was higher expression of CCR2 and CCR5 proteins in the group with Diabetes at the initial visit for classical, intermediate, and nonclassical monocytes, with no differences for CX3CR1 (CCR2: p = 0.004; p = 0.026; p = 0.024; CCR5: 0.045; p = 0.045; p = 0.013; CX3CR1: p = 0.424; p = 0.944; p = 0.392, respectively), without differences after the end of treatment. Concerning each group separately, there were reductions in the expression of CCR2 as well as CCR5 in classical, intermediate, and nonclassical monocytes, and reduction of CX3CR1 in classical monocytes after treatment in the group with Diabetes (p = 0.003; p = 0.006; p = 0.039; p = 0.007; p = 0.006; p = 0.004; p = 0.019, respectively), without differences in the group without Diabetes. The expression of the chemokine receptors CCR2 and CCR5, in patients with Periodontitis associated with Diabetes, is favorably modified after the end of the non-surgical periodontal treatment.

Asunto(s)

Diabetes Mellitus , Periodontitis , Humanos , Monocitos/metabolismo , Proyectos Piloto , Receptores CCR2/genética , Receptores CCR2/metabolismo , Receptores CCR5/genética , Receptores CCR5/metabolismo , Diabetes Mellitus/metabolismo , Periodontitis/terapia , Periodontitis/metabolismo , Receptor 1 de Quimiocinas CX3C/genética , Receptor 1 de Quimiocinas CX3C/metabolismo

RESUMEN

OBJECTIVE: To evaluate the effects of magnifying the damage caused by obesity induced by monosodium glutamate, using a model of maternal periodontitis, on the structure of the anterior tibialis muscle of the offspring. MATERIALS AND METHODS: Twenty-four female Wistar rats were divided into four experimental groups: control (n = 6), obese (n = 6), control with periodontitis (n = 6) and obese with periodontitis (n = 6). At 78 days of life, the rats were mated with males without any experimental intervention. The offspring of these rats (n = 1/L), at 120 days of life, were weighed and measured, then euthanized. Plasma was collected for analysis of cytokines IL-6, IL-10, IL-17 and TNF-α. Adipose tissues were collected and weighed, and the anterior tibial muscle was designated for histomorphological analyses (n = 6/group). RESULTS: Monosodium glutamate offspring showed significant muscle changes, such as a reduction in the size of fibres and neuromuscular junctions, and an increase in the nucleus and capillaries. However, all these changes were more expressed in monosodium glutamate-obese with periodontitis offspring. CONCLUSION: This leads us to suggest a magnifying effect promoted by periodontitis to the damage already well described by monosodium glutamate-obesity, determined by low-intensity inflammation, causing greater muscle damage.

Asunto(s)

Músculo Esquelético , Obesidad , Periodontitis , Ratas Wistar , Glutamato de Sodio , Animales , Glutamato de Sodio/efectos adversos , Femenino , Ratas , Músculo Esquelético/patología , Embarazo , Obesidad/complicaciones , Obesidad/metabolismo , Periodontitis/patología , Periodontitis/metabolismo , Periodontitis/complicaciones , Masculino , Efectos Tardíos de la Exposición Prenatal , Factor de Necrosis Tumoral alfa/metabolismo , Citocinas/metabolismo

RESUMEN

OBJECTIVE: The objective of the study was to evaluate the expression of oxytocin receptors in normal and inflamed gingiva, as well as the effects of systemic administration of oxytocin in bone loss and gum inflammatory mediators in a rat model of experimental periodontitis. BACKGROUND DATA: Current evidence supports the hypothesis of a disbalance between the oral microbiota and the host's immune response in the pathogenesis of periodontitis. Increased complexity of the microbial biofilm present in the periodontal pocket leads to local production of nitrogen and oxygen-reactive species, cytokines, chemokines, and other proinflammatory mediators which contribute to periodontal tissue destruction and bone loss. Oxytocin has been suggested to participate in the modulation of immune and inflammatory processes. We have previously shown that oxytocin, nitric oxide, and endocannabinoid system interact providing a mechanism of regulation for systemic inflammation. Here, we aimed at investigating not only the presence and levels of expression of oxytocin receptors on healthy and inflamed gingiva, but also the effects of oxytocin treatment on alveolar bone loss, and systemic and gum expression of inflammatory mediators involved in periodontal tissue damage using ligature-induced periodontitis. Therefore, anti-inflammatory strategies oriented at modulating the host's immune response could be valuable adjuvants to the main treatment of periodontal disease. METHODS: We used an animal model of ligature-induced periodontitis involving the placement of a linen thread (Barbour flax 100% linen suture, No. 50; size 2/0) ligature around the neck of first lower molars of adult male rats. The ligature was left in place during the entire experiment (7 days) until euthanasia. Animals with periodontitis received daily treatment with oxytocin (OXT, 1000 µg/kg, sc.) or vehicle and/or atosiban (3 mg/kg, sc.), an antagonist of oxytocin receptors. The distance between the cement-enamel junction and the alveolar bone crest was measured in stained hemimandibles in the long axis of both buccal and lingual surfaces of both inferior first molars using a caliper. TNF-α levels in plasma were determined using specific rat enzyme-linked immunosorbent assays (ELISA). OXT receptors, IL-6, IL-1ß, and TNF-α expression were determined in gingival tissues by semiquantitative or real-time PCR. RESULTS: We show that oxytocin receptors are expressed in normal and inflamed gingival tissues in male rats. We also show that the systemic administration of oxytocin prevents the experimental periodontitis-induced increased gum expression of oxytocin receptors, TNF-α, IL-6, and IL-1ß (p < .05). Furthermore, we observed a reduction in bone loss in rats treated with oxytocin in our model. CONCLUSIONS: Our results demonstrate that oxytocin is a novel and potent modulator of the gingival inflammatory process together with bone loss preventing effects in an experimental model of ligature-induced periodontitis.

Asunto(s)

Pérdida de Hueso Alveolar , Periodontitis , Ratas , Masculino , Animales , Oxitocina/uso terapéutico , Oxitocina/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Receptores de Oxitocina/metabolismo , Modelos Animales de Enfermedad , Periodontitis/metabolismo , Encía/metabolismo , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/prevención & control , Pérdida de Hueso Alveolar/etiología , Proceso Alveolar/metabolismo , Mediadores de Inflamación/metabolismo

RESUMEN

BACKGROUND: The relationship between type II diabetes mellitus (DM) and periodontal disease (PD) has been discussed in recent years and may vary according to the patient's location, sex, age and family history. OBJECTIVE: In view of this possible association between periodontitis and DM, this study aimed to evaluate salivary glucose and salivary cortisol levels with periodontitis (staging and degree) in people with type II diabetes compared to non-diabetic individuals. METHODS: This was a case-control study, with 60 participants divided into two groups: DM2- people with type II diabetes (n=30) and NDM- non-diabetic individuals (n=30). For both, a clinical form and periogram were filled out, and blood samples (glycemia, glycated hemoglobin, and cortisol) and saliva (glucose and cortisol) were collected. RESULTS: The diagnosis of periodontitis was 100% in the DM2 group and 80% in the NDM group. As for staging and degree, in the DM2 group, 70% of the participants were in stage IV and 86.67% were in grade C, while in the NDM group, 58.3% of the participants were in stage I and 70.8% were in grade A. Significant differences were observed for the following variables: bleeding to probing and clinical attachment level. The laboratory data presented significant results regarding serum glucose, salivary glucose, and glycated hemoglobin. CONCLUSION: Regarding the influence of salivary glucose and cortisol on periodontal status (staging and degree), these had higher means in the DM2 group when compared to the NDM group. An association of salivary glucose and cortisol levels with the periodontal condition presented by type II diabetic individuals compared to non-diabetic individuals is suggested.

Asunto(s)

Glucemia , Diabetes Mellitus Tipo 2 , Hemoglobina Glucada , Hidrocortisona , Periodontitis , Saliva , Humanos , Estudios de Casos y Controles , Saliva/química , Saliva/metabolismo , Hidrocortisona/análisis , Hidrocortisona/metabolismo , Hidrocortisona/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Masculino , Persona de Mediana Edad , Periodontitis/complicaciones , Periodontitis/metabolismo , Glucemia/análisis , Glucemia/metabolismo , Hemoglobina Glucada/análisis , Adulto , Anciano

RESUMEN

OBJECTIVE: The present study was designed to investigate the role of macrophage migration inhibitory factor (MIF) in the exacerbation of pregestational periodontal disease (PGPD). BACKGROUND: Periodontitis (PT) is a severe stage of periodontal disease characterized by inflammation of the supporting tissues of the teeth, which usually worsens during pregnancy. MIF is a proinflammatory cytokine that is significantly elevated in periodontitis, both at the beginning and at the end of pregnancy. Although periodontitis usually presents with greater severity during pregnancy, the participation of MIF in the evolution of periodontitis has not been established. METHODS: To analyze the relevance of MIF in the exacerbation of PGPD, we employed a model of PGPD in WT and Mif-/- mice, both with a BALB/c genetic background. PT was induced with nylon suture ligatures placed supramarginally around the second upper right molar. For PGPD, PT was induced 2 weeks before mating. We evaluated histological changes and performed histometric analysis of the clinical attachment loss, relative expression of MMP-2 and MMP-13 by immunofluorescence, and relative expression of the cytokines mif, tnf-α, ifn-γ, and il-17 by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Our data revealed that periodontal tissue from PGPD WT mice produced a twofold increase in MIF compared with PT WT mice. Moreover, the evolution of periodontitis in Mif-/- mice was less severe than in PGDP WT mice. Periodontal tissue from Mif-/- mice with PGPD produced 80% less TNF-α and no IFN-γ, as well as 50% lower expression of matrix metalloproteinase (MMP)-2 and 25% less MMP-13 compared to WT PGDP mice. CONCLUSIONS: Our study suggests that MIF plays an important role in the exacerbation of periodontitis during pregnancy and that MIF is partially responsible for the inflammation associated with the severity of periodontitis during pregnancy.

Asunto(s)

Factores Inhibidores de la Migración de Macrófagos , Periodontitis , Animales , Femenino , Ratones , Embarazo , Inflamación/metabolismo , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Metaloproteinasa 13 de la Matriz , Periodontitis/metabolismo , Factor de Necrosis Tumoral alfa

RESUMEN

Periodontitis is an oral-cavity inflammatory disease and is the principal cause associated with tooth loss. Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) are important proteases involved in periodontal tissue destruction. The omega-3 polyunsaturated fatty acids (ω-3 PUFA) have been demonstrated to possess immunoregulatory properties in periodontitis. The aim of the study was to investigate the effects of ω-3 PUFA on inflammation and on the expression of MMP-2 and -9 in a murine periodontitis model. Twenty-four male C57BL/6 mice were divided into control mice (Control), control mice treated with ω-3 PUFA (O3), mice with periodontitis (P), and mice with periodontitis treated with ω-3 PUFA (P + O3). ω-3 PUFA were administered orally once a day for 70 days. Periodontitis in mice was induced by Porphyromonas gingivalis-infected ligature placement around the second maxillary molar. The mice were sacrificed, and blood and maxillary samples were collected. Flow cytometry was used to quantify tumor necrosis factor-alpha (TNFα), interleukin (IL)-2, IL-4, IL-5, and interferon-gamma. Histologic analysis and immunohistochemistry for MMP-2 and -9 were performed. The data were statistically evaluated using analysis of variance (ANOVA) and the Tukey post hoc test. Histological analysis showed that ω-3 PUFA supplementation prevented inflammation and tissue destruction and revealed that bone destruction was more extensive in the P group than in the P + O3 group (p < 0.05). Also, it decreased the serum expressions of TNFα and IL-2 and the tissue expression of MMP-2 and -9 in the periodontitis-induced model (p < 0.05). ω-3 PUFA supplementation prevented alveolar bone loss and periodontal destruction, probably by decreasing the expression of MMP-2 and MMP-9 and its immunoregulatory properties.

Asunto(s)

Ácidos Grasos Omega-3 , Periodontitis , Ratones , Masculino , Animales , Metaloproteinasa 2 de la Matriz , Metaloproteinasa 9 de la Matriz , Ácidos Grasos Omega-3/farmacología , Modelos Animales de Enfermedad , Factor de Necrosis Tumoral alfa , Ratones Endogámicos C57BL , Periodontitis/tratamiento farmacológico , Periodontitis/prevención & control , Periodontitis/metabolismo , Inflamación , Dieta , Porphyromonas gingivalis

RESUMEN

Lipoproteins are immunostimulatory bacterial components suggested to participate in inflammation-induced bone loss in periodontal disease through stimulation of osteoclast differentiation. Toll-like receptor 2 activation by Pam2CSK4 (PAM2), known to mimic bacterial lipoproteins, was previously shown to enhance periodontal bone resorption in mice. The anti-inflammatory cytokine interleukin-4 (IL-4) is a known inhibitor of RANKL-induced bone resorption in vitro. Here, we have investigated whether IL-4 could decrease PAM2-induced periodontal bone loss and osteoclastogenesis in vivo. In a model of periodontitis induced by gingival injections of PAM2 in mice, concomitant injections of IL-4 reduced bone loss. Histologically, IL-4 reduced the recruitment of inflammatory cells and the formation of TRAP+ osteoclasts stimulated by PAM2. Mouse bone marrow macrophages (BMMs) and neonatal calvarial osteoblasts were used to assess the effect of IL-4 on PAM2-induced osteoclastogenesis in vitro. In RANKL-primed BMMs stimulated by PAM2 Nfatc1, Ctsk, and Acp5 gene expression was up-regulated and resulted in robust formation of TRAP+ multinucleated osteoclasts, effects which were impaired by IL-4. These effects were mediated by impairment in PAM2-induced c-fos expression. In primary calvarial osteoblast cultures, IL-4 decreased PAM2-induced Tnfsf11 (encoding RANKL) mRNA and enhanced Tnfrsf11b (encoding OPG) expression. Our data demonstrate that the osteoprotective effect by IL-4 on lipoprotein-induced periodontal disease occurs through the inhibition of osteoclastogenesis by three mechanisms, one by acting directly on osteoclast progenitors, another by acting indirectly through decreasing the expression of osteoclast-regulating cytokines in osteoblasts and a third by decreasing inflammation.

Asunto(s)

Pérdida de Hueso Alveolar , Resorción Ósea , Periodontitis , Animales , Ratones , Interleucina-4/metabolismo , Osteoclastos/metabolismo , Resorción Ósea/metabolismo , Citocinas/metabolismo , Periodontitis/metabolismo , Pérdida de Hueso Alveolar/metabolismo , Inflamación/metabolismo , Ligando RANK/metabolismo , Diferenciación Celular

RESUMEN

BACKGROUND AND OBJECTIVE: There is no clear understanding of molecular events occurring in the periodontal microenvironment during clinical disease progression. Our aim was to explore qualitative and quantitative differences in gingival crevicular fluid (GCF) protein profiles from patients diagnosed with periodontitis between non-progressive and progressive periodontal sites. METHODS: Five systemically healthy patients diagnosed with periodontitis were monitored weekly in their progression of the disease and GCF samples from 10 candidate sites were obtained. Two groups of five sites, matched from an equal number of teeth, were selected from the five patients: Progression (PG) and Non-Progression (NP). Global protein identification was performed with high-throughput proteomic approaches and label-free analysis determined their relative abundances. Proteins were identified by Proteome Discoverer v2.4 and searched against human SwissProt protein databases. Enrichment bioinformatic analyses were performed in STRING-DB and ShinyGO environment. RESULTS: 1504 and 1500 proteins were identified in NP and PG respectively. Forty-eight proteins were exclusively identified in PG, while 52 were identified in NP. Moreover, 35 proteins were more abundant in PG and 29 proteins in NP (twofold change, p < .05). The NP group was mainly represented by proteins from "response to biotic stimuli and other organisms," "processes of cell death regulation," "peptidase regulation," "protein ubiquitination," and "ribosomal activity" GO categories. The most represented GO categories of the PG group were "assembly of multiprotein complexes," "catabolic processes," "lipid metabolism," and "binding to hemoglobin and haptoglobin." CONCLUSIONS: There are quantitative and qualitative differences in the proteome of GCF from periodontal sites according to the status of clinical progression of periodontitis. Progressive periodontitis sites are characterized by a protein profile associated with catabolic processes, immune response, and response to cellular stress, while stable periodontitis sites show a protein profile mainly related to wound repair and healing processes, cell death regulation, and chaperone-mediated autophagy. Understanding the etiopathogenic role of these profiles in progressive periodontitis may help to develop new diagnostic and therapeutic approaches.

Asunto(s)

Periodontitis , Proteoma , Humanos , Líquido del Surco Gingival/química , Proteómica , Periodontitis/metabolismo , Progresión de la Enfermedad

RESUMEN

This study aimed to compare the proteomic profile of stimulated and unstimulated saliva samples from pregnant women with/without obesity and periodontitis. Pregnant women were allocated into four groups: with obesity and periodontitis (OP); with obesity but without periodontitis (OWP); with normal BMI but with periodontitis (NP); with normal BMI and without periodontitis (NWP). Stimulated saliva (SS) and unstimulated saliva (US) samples were collected, and salivary proteins were extracted and individually processed by proteomic analysis (nLC-ESI-MS/MS). Proteins involved with the immune response process, antioxidant activity, and retina homeostasis were decreased or absent in SS samples from all groups (i.e., Antileukoproteinase, Lysozyme C, Alpha-2-macroglobulin-like protein 1, Heat shock proteins-70 kDa 1-like, 1A, 1B, 6, Heat shock-related 70 kDa protein 2, Putative Heat shock 70 kDa protein 7, Heat shock cognate 71 kDa). Additionally, proteins related to the carbohydrate metabolic process and glycolytic and glucose metabolic process were absent in SS, mainly from OP and OWP (i.e., Frutose-bisphosphate aldose A, Glusoce-6-phosphate isomerase, Pyruvate kinase). Saliva stimulation decreased important proteins involved with immune response and inflammation process in all groups. Unstimulated salivary samples seem to be the best choice for the proteomic approach in pregnant women.

Asunto(s)

Periodontitis , Mujeres Embarazadas , Humanos , Femenino , Embarazo , Espectrometría de Masas en Tándem , Saliva/metabolismo , Proteómica , Periodontitis/metabolismo , Obesidad/metabolismo

RESUMEN

BACKGROUND: This study evaluated the systemic (intestine and adipose tissue) and local (periodontal tissues) impact of probiotic therapy in rats with metabolic syndrome (MS) associated or not with periodontitis (PE). METHODS: Forty-eight rats received a high-fat diet for induction of MS for 16 weeks. They were subdivided into groups with (+) and without (-) PE, receiving (*) or not (**) receiving probiotics (PROB): MS (-**), MSP (-*), MSPE (+**), and MSPEP (+*). PROB administration (Bifidobacterium animalis subsp. lactis HN019) started on the 8th week of the study and PE was induced on the 14th week by placing ligature on the animals' lower first molars. Euthanasia occurred in the 16th week. Biomolecular, immunoenzymatic assays, and histomorphometric analyses were performed. The data obtained were statistically analyzed (ANOVA, Tukey, p < 0.05). RESULTS: The MSPEP group exhibited reduced alveolar bone loss when compared with the MSPE group, as well as lower levels of hepatic steatosis and proteinuria (p < 0.05). In the intestinal environment, the MSPE group exhibited significantly lower villus height and crypt depth, as well as a greater increase in Bacillota when compared with the MSPEP group (p < 0.05). The MSPEP group showed lower adipokine gene expression (LEPR, NAMPT, and FABP4) in adipose tissue than the MSPE group (p < 0.05). CONCLUSION: The probiotic B. lactis HN019 reduced the severity of experimental periodontitis and modulated the expression of lipogenic genes and intestinal morphological and microbiological parameters in rats with MS.

Asunto(s)

Bifidobacterium animalis , Síndrome Metabólico , Periodontitis , Probióticos , Ratas , Animales , Síndrome Metabólico/complicaciones , Periodontitis/terapia , Periodontitis/metabolismo , Intestinos/microbiología , Probióticos/uso terapéutico , Probióticos/farmacología

RESUMEN

During orthodontic treatment, diverse cytokines, enzymes, and osteolytic mediators produced within the teeth surrounding periodontal tissues determine the rate of alveolar bone remodeling and consequent teeth movement. In patients with teeth presenting reduced periodontal support, periodontal stability should be ensured during orthodontic treatment. Thus, therapies based on the application of low-intensity intermittent orthodontic forces are recommended. To determine if this kind of treatment is periodontally well tolerated, this study aimed to analyze the production of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), interleukin (IL)-6, IL-17A, and matrix metalloproteinase (MMP)-8 in periodontal tissues of protruded anterior teeth with reduced periodontal support and undergoing orthodontic treatment. Patients with periodontitis-associated anterior teeth migration received non-surgical periodontal therapy and a specific orthodontic treatment involving controlled low-intensity intermittent orthodontic forces. Samples were collected before periodontitis treatment, after periodontitis treatment, and at 1 week to 24 months of the orthodontic treatment. During the 2 years of orthodontic treatment, no significant differences were detected in the probing depth, clinical attachment level, supragingival bacterial plaque, and bleeding on probing. In line with this, the gingival crevicular levels of RANKL, OPG, IL-6, IL-17A, and MMP-8 did not vary between the different evaluation time-points of the orthodontic treatment. When compared with the levels detected during the periodontitis, the RANKL/OPG ratio was significantly lower at all the analyzed time-points of the orthodontic treatment. In conclusion, the patient-specific orthodontic treatment based on intermittent orthodontic forces of low intensities was well tolerated by periodontally compromised teeth with pathological migration.

Asunto(s)

Resorción Ósea , Periodontitis , Humanos , Resorción Ósea/metabolismo , Citocinas , Encía , Líquido del Surco Gingival , Interleucina-17 , Interleucina-6 , Osteoprotegerina , Periodontitis/metabolismo , Periodontitis/terapia , Ligando RANK/análisis , Ortodoncia

RESUMEN

Porphyromonas gingivalis is a keystone pathogen associated with periodontitis development, a chronic inflammatory pathology characterized by the destruction of the supporting teeth structure. Macrophages are recruited cells in the inflammatory infiltrate from patients with periodontitis. They are activated by the P. gingivalis virulence factors arsenal, promoting an inflammatory microenvironment characterized by cytokine production (TNF-α, IL-1ß, IL-6), prostaglandins, and metalloproteinases (MMPs) that foster the tissular destruction characteristic of periodontitis. Furthermore, P. gingivalis suppresses the generation of nitric oxide, a potent antimicrobial molecule, through its degradation, and incorporating its byproducts as a source of energy. Oral antimicrobial peptides can contribute to controlling the disease due to their antimicrobial and immunoregulatory activity, which allows them to maintain homeostasis in the oral cavity. This study aimed to analyze the immunopathological role of macrophages activated by P. gingivalis in periodontitis and suggested using antimicrobial peptides as therapeutic agents to treat the disease.

Asunto(s)

Periodontitis , Porphyromonas gingivalis , Humanos , Péptidos Antimicrobianos , Macrófagos/metabolismo , Macrófagos/patología , Periodontitis/metabolismo , Inmunomodulación

RESUMEN

AIM: To compare the salivary proteomic profile of periodontitis-affected (PA) parents and their offspring to periodontally healthy (PH) dyads in the pursuit of possible biomarkers for early diagnosis of this disease. MATERIALS AND METHODS: Unstimulated saliva samples collected from 17 pairs of PA or PH individuals and their children were submitted to mass spectrometric analyses followed by proteomic analyses. Primary PA fibroblasts were triggered towards having an inflammatory response, and an immunoenzymatic assay of its supernatant was performed to validate the obtained data. RESULTS: ANXA1, KRT4, GSTP1, HPX, A2M and KRT13 were lower in PA parents and their children, and IGHG1, CSTB, KRT9, SMR3B, IGHG4 and SERPINA1 were higher. ANXA1 presented the highest fold change, 7.1 times less produced in children of PA parents, and was selected as a potential biomarker for periodontitis. The in vitro assay also showed lower ANXA1 production by cells of PA patients. CONCLUSION: Before any clinical sign of periodontal loss, descendants of PA patients have an altered proteomic profile compared to PH individuals, presenting a lower abundance of ANXA1. This protein is suggested as a potential biomarker for periodontitis.

Asunto(s)

Anexina A1 , Periodontitis , Niño , Humanos , Anexina A1/análisis , Anexina A1/metabolismo , Biomarcadores/metabolismo , Periodontitis/diagnóstico , Periodontitis/metabolismo , Proteómica , Saliva/química

RESUMEN

OBJECTIVE: Abnormal complement activation is associated with periodontitis. W54011 is a novel non-peptide C5aR antagonist (C5aRA) that exhibits favorable anti-inflammatory effects in various inflammatory models. However, whether W54011 inhibits periodontitis has not yet been fully elucidated. To address this, we have investigated the probable anti-inflammatory mechanism of W54011 in LPS-treated inflammation in human gingival fibroblasts (HGFs). METHODOLOGY: HGFs were isolated from healthy gingival tissue samples using the tissue block method and were identified with immunofluorescence staining. The CCK8 assay and reverse transcription-PCR (RT-PCR) were used to select the optimal induction conditions for Lipopolysaccharide (LPS) and C5aRA (according to supplementary data S1, S2 and S3). The levels of inflammatory cytokines, C5aR, and the activation of NF-κB/MAPK signaling pathways were determined by RT-quantitative PCR (RT-qPCR) and Western blotting. RESULTS: Immunofluorescence results showed that vimentin and FSP-1 were positive in HGFs and Keratin was negative in HGFs. Immunofluorescence staining demonstrated that C5aRA inhibited LPS-stimulated nuclear translocation of p-p65. RT-qPCR and Western blotting showed that C5aRA reduced the expression of IL-1ß, IL-6, TNF-α, C5aR, p-p65, p-IκBα, p-JNK, p-c-JUN, and TLR4 in LPS-induced HGFs. CONCLUSION: These findings suggested that C5aRA attenuated the release of inflammatory cytokines in LPS-induced HGFs by blocking the activation of the NF-κB and MAPK signaling pathways.

Asunto(s)

FN-kappa B , Periodontitis , Humanos , Lipopolisacáridos/farmacología , Lipopolisacáridos/metabolismo , Transducción de Señal , Inflamación , Citocinas/metabolismo , Antiinflamatorios/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Periodontitis/tratamiento farmacológico , Periodontitis/metabolismo , Fibroblastos

RESUMEN

Cinnamaldehyde is a natural product with anti-inflammatory and immune-modulatory properties, known to regulate host responses to bacterial stimuli. This study aimed to investigate the effects of cinnamaldehyde on ligature-induced periodontitis in rats, and its impact on the modulation of human peripheral blood mononuclear cells (PBMC). Male Wistar rats were assigned into three groups:i) control: no ligature + vehicle; ii) ligature: ligature + vehicle; and iii) ligature + cinnamaldehyde (50 mg/kg); all treatments by daily oral gavage. After 14 days of induced periodontitis, the hemimandibles were collected for bone loss evaluation. The gingival levels of IL-1ß, MMP-9 and iNOS mRNA were evaluated. Nitric oxide (NO) was measured in both rat saliva and plasma. PBMC were stimulated with Aggregatibacter actinomycetemcomitans (Aa) in the presence or absence of cinnamaldehyde (5, 20 e 40 µM), and cytokine production was quantified in cell supernatant. Proliferating lymphocytes were taken for flow cytometer reading, while culture supernatants were used for IFN-γ and IL-10 assessment. The ligature group had both increased alveolar bone loss and gingival expression of IL-1ß, MMP-9 and iNOS compared to the control group. All parameters were attenuated by cinnamaldehyde treatment. Lower salivary but not plasma NO was detected in the cinnamaldehyde compared to the ligature group. Aa-stimulated PBMCs treated with cinnamaldehyde produced less IL-1ß; the compound also attenuated lymphocyte proliferation in a dose-dependent manner, as well as cell IL-10 production. Cinnamaldehyde treatment reduced periodontal bone loss, and downregulated key inflammatory mediators and human PBMC responses, pointing to novel potential therapeutic effects of this compound.

Asunto(s)

Pérdida de Hueso Alveolar , Periodontitis , Humanos , Ratas , Masculino , Animales , Ratas Wistar , Leucocitos Mononucleares/metabolismo , Interleucina-10/uso terapéutico , Metaloproteinasa 9 de la Matriz , Periodontitis/metabolismo , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/metabolismo , Modelos Animales de Enfermedad

RESUMEN

AIMS: Increased cardiovascular disease risk underlies elevated rates of mortality in individuals with periodontitis. A key characteristic of those with increased cardiovascular risk is endothelial dysfunction, a phenomenon synonymous with deficiencies of bioavailable nitric oxide (NO), and prominently expressed in patients with periodontitis. Also, inorganic nitrate can be reduced to NO in vivo to restore NO levels, leading us to hypothesise that its use may be beneficial in reducing periodontitis-associated endothelial dysfunction. Herein we sought to determine whether inorganic nitrate improves endothelial function in the setting of periodontitis and if so to determine the mechanisms underpinning any responses seen. METHODS AND RESULTS: Periodontitis was induced in mice by placement of a ligature for 14 days around the second molar. Treatment in vivo with potassium nitrate, either prior to or following establishment of experimental periodontitis, attenuated endothelial dysfunction, as determined by assessment of acetylcholine-induced relaxation of aortic rings, compared to control (potassium chloride treatment). These beneficial effects were associated with a suppression of vascular wall inflammatory pathways (assessed by quantitative-PCR), increases in the anti-inflammatory cytokine interleukin (IL)-10 and reduced tissue oxidative stress due to attenuation of xanthine oxidoreductase-dependent superoxide generation. In patients with periodontitis, plasma nitrite levels were not associated with endothelial function indicating dysfunction. CONCLUSION: Our results suggest that inorganic nitrate protects against, and can partially reverse pre-existing, periodontitis-induced endothelial dysfunction through restoration of nitrite and thus NO levels. This research highlights the potential of dietary nitrate as adjunct therapy to target the associated negative cardiovascular outcomes in patients with periodontitis.

Asunto(s)

Periodontitis , Enfermedades Vasculares , Ratones , Animales , Nitratos , Nitritos/metabolismo , Óxido Nítrico/metabolismo , Periodontitis/tratamiento farmacológico , Periodontitis/metabolismo , Enfermedades Vasculares/metabolismo , Endotelio Vascular

RESUMEN

AIM: The aim of this study was to evaluate the effects of Bdellovibrio bacteriovorus HD100 on experimental periodontitis (EP) in rats. METHODS: Thirty-two rats were divided into four groups: control, C-HD100 (B. bacteriovorus), EP, and EP-HD100. On day 0, EP was induced by the placement of cotton ligatures around the mandibular first molars (MFMs) in the EP and EP-HD100 groups. In the C-HD100 and EP-HD100 groups, suspensions containing 1 × 109  PUF/ml of B. bacteriovorus HD100 were topically administered to the subgingival region of MFMs on days 0, 3, and 7. Animals were euthanized on day 14. Morphometrics analyses were performed in hemimandibles. The levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, IL-10, IL-1ß, transforming growth factor beta (TGF-ß), macrophage colony-stimulating factor (M-CSF) and regulated on activation and normal T cell expressed and secreted (RANTES) were determined by enzymatic immunoassays in gingival tissues. Beta defensin (BD)-1, BD-2, and BD-3, Toll-like receptors (TLR)-2 and TLR-4, and a cluster of differentiation (CD)-4, CD-8 and CD-57 were analyzed by immunohistochemistry in hemimandibles. Data were statistically analyzed. RESULTS: The EP group showed greater alveolar bone loss than EP-HD100 (p < .05). The EP-HD100 group showed higher levels of MCP-1, RANTES, IL-10, and TGF-ß, lower levels of TNF-α than the EP group (p < .05). No differences were observed in IL-1ß, IL-6, and M-CSF levels between EP and EP-HD100 groups. The C-HD100 group had higher IL-6, TNF-α, RANTES, and MCP-1 levels than the control group (p < .05). Regarding BD, the EP-HD100 group showed a larger immunolabeling pattern for BD-1, BD-2, and BD-3 than the EP group (p < .05). No significant differences in the immunolabeling pattern were observed for TLR-2, TLR-4, CD-4, CD-8, and CD-57 between EP and EP-HD100 groups. CONCLUSION: The topical use of B. bacteriovorus HD100 reduces alveolar bone loss, increases expression of BD, and modulates the cytokines levels on periodontal tissues in rats with EP.

Asunto(s)

Pérdida de Hueso Alveolar , Bdellovibrio bacteriovorus , Periodontitis , Ratas , Animales , Ratas Wistar , Interleucina-10 , Bdellovibrio bacteriovorus/metabolismo , Factor Estimulante de Colonias de Macrófagos , Receptor Toll-Like 4 , Interleucina-6 , Factor de Necrosis Tumoral alfa/metabolismo , Pérdida de Hueso Alveolar/patología , Periodontitis/metabolismo , Factor de Crecimiento Transformador beta