Casp11 Deficiency Alters Subgingival Microbiota and Attenuates Periodontitis.

Periodontitis (PD) is the primary cause of tooth loss in adults. Porphyromonas gingivalis (P.g), a keystone pathogen, has been identified as a crucial contributor to this process. Pyroptosis activation in PD is acknowledged, with accumulating evidence underscoring the crucial role of Caspase-11 (described as Caspase-4/5 in humans)-mediated noncanonical pyroptosis. However, the mechanism behind its impact on PD remains unclear. In this study, we delved into the interplay between the Caspase-11-mediated noncanonical pyroptosis, subgingival microbiota alteration, and macrophage polarization. Clinical samples from PD patients revealed heightened expression of Caspase-4, gasdermin-D, and their active fragments, pointing to the activation of the noncanonical pyroptosis. Single-cell sequencing analysis linked Caspase-4 with gingival macrophages, emphasizing their involvement in PD. In vitro cell experiments confirmed that P.g-induced pyroptosis was activated in macrophages, with Casp11 deficiency attenuating these effects. In an experimental PD mouse model, Casp11 deficiency led to an alteration in subgingival microbiota composition and reduced alveolar bone resorption. Casp11-/- mice cohousing with wild-type mice confirmed the alteration of the subgingival microbiota and aggravated the alveolar bone resorption. Notably, Casp11 deficiency led to decreased M1-polarized macrophages, corresponding with reduced alveolar bone resorption, uncovering a connection between subgingival microbiota alteration, macrophage M1 polarization, and alveolar bone resorption. Taken together, we showed that Caspase-11 fulfilled a crucial role in the noncanonical pyroptosis in PD, potentially influencing the subgingival microbiota and linking to M1 polarization, which was associated with alveolar bone resorption. These findings underscored the pivotal role of the Caspase-11-mediated noncanonical pyroptosis in PD pathogenesis and may provide critical insights into potential therapeutic avenues for mitigating PD.

PINK1 restrains periodontitis-induced bone loss by preventing osteoclast mitophagy impairment.

The oral colonization of periodontal pathogens onto gingival tissues establishes hypoxic microenvironment, often disrupting periodontal homeostasis in conjunction with oxidative stress. The association between reactive oxygen species (ROS) and osteolytic periodontitis have been suggested by recent studies. PTEN-induced kinase 1 (PINK1), a mitochondrial serine/threonine kinase, is an essential protein for mitochondrial quality control as it protects cells from oxidative stress by promoting degradation of damaged mitochondria through mitophagy. However, the pathophysiological roles of PINK1 in osteoclast-mediated bone loss have not been explored. Here we aimed to determine whether PINK1 plays a role in the regulation of osteoclastogenesis and alveolar bone resorption associated with periodontitis. C57BL/6 wild type (WT) and Pink1 knockout (KO) mice were subjected to ligature-induced periodontitis (LIP), and alveolar bones were evaluated by µCT-analysis and tartrate-resistant acid phosphatase (TRAP) staining. The µCT-analysis showed that bone volume fraction and travecular thickness were lower in Pink1 KO compared to WT mice. The number of TRAP-positive osteoclasts was markedly increased in the periodontal tissues of Pink1 KO mice with LIP. The genetic silencing or deletion of Pink1 promoted excessive osteoclast differentiation and bone resorption in vitro, as respectively indicated by TRAP staining and resorption pits on dentin slices. PINK1 deficiency led to mitochondrial instabilities as indicated by confocal microscopy of mitochondrial ROS, mitochondrial oxygen consumption rate (OCR) analysis, and transmission electron microscopy (TEM). Consequently, a significant increase in Ca2+-nuclear factor of activated T cells 1 (NFATc1) signaling was also found. On the other hand, restoration of mitophagy and autophagy by spermidine (SPD) treatment and the resolution of oxidative stress by N-acetyl-l-cysteine (NAC) treatment protected PINK1 deficiency-induced excessive generation of osteoclasts. Taken together, our findings demonstrate that PINK1 is essential for maintaining mitochondrial homeostasis during osteoclast differentiation. Therefore, targeting PINK1 may provide a novel therapeutic strategy for severe periodontitis with fulminant osteolysis.

Modelling time-varying risk factors of tooth loss: Results from joint model compared with extended Cox regression model.

AIM: To illustrate the use of joint models (JMs) for longitudinal and survival data in estimating risk factors of tooth loss as a function of time-varying endogenous periodontal biomarkers (probing pocket depth [PPD], alveolar bone loss [ABL] and mobility [MOB]). MATERIALS AND METHODS: We used data from the Veterans Affairs Dental Longitudinal Study, a longitudinal cohort study of over 30 years of follow-up. We compared the results from the JM with those from the extended Cox regression model which assumes that the time-varying covariates are exogenous. RESULTS: Our results showed that PPD is an important risk factor of tooth loss, but each model produced different estimates of the hazard. In the tooth-level analysis, based on the JM, the hazard of tooth loss increased by 4.57 (95% confidence interval [CI]: 2.13-8.50) times for a 1-mm increase in maximum PPD, whereas based on the extended Cox model, the hazard of tooth loss increased by 1.60 (95% CI: 1.37-1.87) times. CONCLUSIONS: JMs can incorporate time-varying periodontal biomarkers to estimate the hazard of tooth loss. As JMs are not commonly used in oral health research, we provide a comprehensive set of R codes and an example dataset to implement the method.

Infrared laser therapy decreases systemic oxidative stress and inflammation in hypercholesterolemic mice with periodontitis.

BACKGROUND: Near-infrared irradiation photobiomodulation (NIR-PBM) has been successfully used in periodontal treatment as an adjuvant tool to locally improve cell function and regeneration. Although the relationship between periodontitis and systemic disease constitutes an important aspect of periodontal clinical research, the systemic effects of NIR-PBM in periodontitis are not well known. In this study, we aimed to investigate the effects of NIR-PBM on systemic oxidative stress and inflammation in an apolipoprotein E (ApoE) knockout mouse model of periodontal disease (PD). METHODS: We evaluated alveolar bone loss by measuring the distance from the cementoenamel junction (CEJ) to the alveolar bone crest (ABC), reactive oxygen species (ROS) production in blood cells, inflammatory activity, plasma cholesterol levels, and lipid peroxidation levels in three experimental groups: (1) ApoEC, control group without intervention; (2) ApoEP, first molar ligation-induced periodontitis for 4 weeks; and (3) ApoEP + PBM, exposed to 808 nm continuous wave, ø ~ 3 mm2, 100 mW, 60 s of NIR-PBM for 7 consecutive days after 4 weeks of periodontitis. At the end of the experimental protocols, ApoEP mice presented significantly increased alveolar bone loss, ROS production, inflammatory activity, plasma cholesterol, and lipid peroxidation levels compared to the ApoEC group (P < 0.05). NIR-PBM for 7 days in the ApoEP + PBM mice significantly decreased systemic ROS production, inflammatory response, plasma cholesterol, and lipid peroxidation levels, similar to those found in the ApoEC group (P > 0.05). However, it was not capable of preventing alveolar bone loss (P > 0.05 compared to ApoEP mice). CONCLUSION: A 7-day treatment with NIR-PBM effectively reduces systemic oxidative stress and inflammatory parameters in hypercholesterolemic mice with PD. However, more studies with longer evaluation times are needed to confirm the systemic effects of locally applied NIR-PBM on PD associated with hypercholesterolemia.

Effect of artesunate on cardiovascular complications in periodontitis in a type I diabetes rat model and related mechanisms.

PURPOSE: Both cardiovascular disease and periodontitis are complications of diabetes that have a great impact on human life and health. Our previous research found that artesunate can effectively improve cardiovascular disease in diabetes and has an inhibitory effect on periodontal disease. Therefore, the present study aimed to explore the potential therapeutic possibility of artesunate in the protection against cardiovascular complications in periodontitis with type I diabetes rats and to elucidate the possible underlying mechanisms. METHODS: Sprague‒Dawley rats were randomly divided into the healthy, diabetic, periodontitis, diabetic with periodontitis, and artesunate treatment groups (10, 30, and 60 mg/kg, i.g.). After artesunate treatment, oral swabs were collected and used to determine changes in the oral flora. Micro-CT was performed to observe changes in alveolar bone. Blood samples were processed to measure various parameters, while cardiovascular tissues were evaluated by haematoxylin-eosin, Masson, Sirius red, and TUNEL staining to observe fibrosis and apoptosis. The protein and mRNA expression levels in the alveolar bone and cardiovascular tissues were detected using immunohistochemistry and RT‒PCR. RESULTS: Diabetic rats with periodontitis and cardiovascular complications maintained heart and body weight but exhibited reduced blood glucose levels, and they were able to regulate blood lipid indicators at normal levels after artesunate treatment. The staining assays suggested that treatment with 60 mg/kg artesunate has a significant therapeutic effect on myocardial apoptotic fibrosis. The high expression of NF-κB, TLR4, VEGF, ICAM-1, p38 MAPK, TGF-ß, Smad2, and MMP9 in the alveolar bone and cardiovascular tissue in the type I diabetes and type I diabetes with periodontitis rat models was reduced after treatment with artesunate in a concentration-dependent manner. Micro-CT showed that treatment with 60 mg/kg artesunate effectively alleviated alveolar bone resorption and density reduction. The sequencing results suggested that each model group of rats had vascular and oral flora dysbiosis, but artesunate treatment could correct the dysbacteriosis. CONCLUSIONS: Periodontitis-related pathogenic bacteria cause dysbiosis of the oral and intravascular flora in type I diabetes and aggravate cardiovascular complications. The mechanism by which periodontitis aggravates cardiovascular complications involves the NF-κB pathway, which induces myocardial apoptosis, fibrosis, and vascular inflammation.

Risk indicators of long-term outcome of implant therapy in patients with a history of severe periodontitis or no history of periodontitis: A retrospective cohort study.

OBJECTIVE: The aim of this retrospective cohort study was to assess factors associated with peri-implant disease in partially edentulous patients with a history of severe periodontitis or no history of periodontitis. METHODS: Partially edentulous patients with a history of severe periodontitis/without history of periodontitis who received implant surgery within the past 6 to 8 years were recalled. Clinical and radiographic examinations were recorded. Periodontal probing depth, marginal bone loss (MBL) and peri-implantitis were considered as the primary outcome and peri-implant bleeding on probing (BOP) was considered as the secondary outcome. The following criteria were considered as the predictors, as well: history of severe periodontitis, gender, age, smoking, brushing frequency, recall interval, full-mouth plaque score, full-mouth bleeding score, splinted prosthesis, open/tight interproximal contact, width of keratinized mucosa, mucosal thickness, implants placed in the grafted bone and implant type. Univariate and multivariate regression analyses were utilized. RESULTS: A total of 88 patients (186 implants) fulfilled the study. Forty-seven patients (108 implants) had a history of severe periodontitis and 41 patients (78 implants) had no history of periodontitis. There was a higher chance of peri-implantitis in patients with a history of severe periodontitis (OR = 11.13; p = 0.045), implants with lack of peri-implant KM (<2 mm) and implants placed in the grafted bone (OR = 14.94, p < 0.001; OR = 4.93, p = 0.047). The risk of peri-implant MBL ≥3 mm was higher in patients with greater FMBS (OR = 1.20; p < 0.001). The chance of peri-implant BOP was independently higher in patients who brushed their teeth at most once per day (OR = 3.20; p = 0.04), higher FMBS (OR = 1.16; p < 0.001) and irregular recall visits (OR = 15.34; p = 0.001). CONCLUSIONS: Partially edentulous patients with the history of severe periodontitis, lack of peri-implant KM and implants placed in bone-grafted sites expressed higher probability of peri-implantitis. In addition, inadequate frequency of brushing (at most once daily) and irregular recall visits were associated with greater chance of peri-implant BOP.

Periodontitis is associated with an increased hazard of mortality in a longitudinal cohort study over 50 years.

AIM: To evaluate the association between periodontal disease and all-cause mortality in a longitudinal cohort study over 50 years. MATERIALS AND METHODS: Participants (N = 1156) in the Veterans Affairs Dental Longitudinal Study, aged 25-85 years at enrollment in 1968, received comprehensive medical and oral exams approximately every 3 years through 2007. Periodontal status was defined using person-level, mean whole-mouth radiographic alveolar bone loss (ABL) scores using a five-point Schei ruler, each unit representing 20% increments of ABL. Time-varying Cox regression models estimated hazard ratios (HRs) for the association between continuous and categorical ABL and mortality, adjusting for covariates. RESULTS: Each one-unit increase in mean ABL score was associated with a 14% increase in the hazard of mortality (adjusted HR = 1.14, 95% confidence interval [CI] 1.02, 1.27). When assessed categorically, HRs for average scores of 2 to <3 and 3 to ≤5 showed increasing associations with hazard of mortality, relative to 0 to <1 (adjusted HR = 1.17, 95% CI 0.94, 1.46; and HR = 1.65, 95% CI 0.94, 2.85, respectively). By contrast, we observed null associations for average scores of 1 to <2 relative to 0 to <1 (adjusted HR = 1.00, 95% CI 0.86, 1.17). CONCLUSIONS: Time-varying periodontal status assessed using radiographic ABL was positively associated with all-cause mortality even after confounder adjustment.

Severe alveolar bone resorption in Felty syndrome: a case report.

BACKGROUND: Felty syndrome is defined by three conditions: neutropenia, rheumatoid arthritis, and splenomegaly. Neutropenia associated with pancytopenia may further affect the dental condition of a patient. Periodontal treatment and surgery in patients with Felty syndrome necessitates cooperation with a hematologist. Here we present a case of a patient with Felty syndrome who was initially referred to the oral surgery hospital attached to the School of Dentistry for extensive periodontitis. She was effectively treated in collaboration with the hematology department. CASE PRESENTATION: A 55-year-old Asian woman visited our department with concerns of worsening tooth mobility, discomfort, and spontaneous gingival bleeding. Initial periodontal examination revealed generalized severe periodontitis (Stage IV Grade C) resulting from leukopenia/neutropenia and poor oral hygiene. A thorough treatment strategy involving comprehensive dental procedures, such as multiple extractions and extensive prosthetic treatment, was implemented. Following the diagnosis of Felty syndrome, the patient was started on treatment with oral prednisolone 40 mg/day, which effectively controlled the disease. Furthermore, there was no recurrence of severe periodontitis after the periodontal treatment. CONCLUSIONS: Dentists and physicians should be aware that immunocompromised individuals with pancytopenia and poor oral hygiene are at risk of developing extensive periodontitis. If their susceptibility to infection and pancytopenia-related bleeding can be managed, such patients can still receive comprehensive dental treatment, including teeth extractions and periodontal therapy. Cooperation among the dentist, hematologist, and patient is necessary to improve treatment outcomes and the patient's quality of life.

Osteoporosis and Alveolar Bone Health in Periodontitis Niche: A Predisposing Factors-Centered Review.

Periodontitis is a periodontal inflammatory condition that results from disrupted periodontal host-microbe homeostasis, manifested by the destruction of tooth-supporting structures, especially inflammatory alveolar bone loss. Osteoporosis is characterized by systemic deterioration of bone mass and microarchitecture. The roles of many systemic factors have been identified in the pathogenesis of osteoporosis, including endocrine change, metabolic disorders, health-impaired behaviors and mental stress. The prevalence rate of osteoporotic fracture is in sustained elevation in the past decades. Recent studies suggest that individuals with concomitant osteoporosis are more vulnerable to periodontal impairment. Current reviews of worse periodontal status in the context of osteoporosis are limited, mainly centering on the impacts of menopausal and diabetic osteoporosis on periodontitis. Herein, this review article makes an effort to provide a comprehensive view of the relationship between osteoporosis and periodontitis, with a focus on clarifying how those risk factors in osteoporotic populations modify the alveolar bone homeostasis in the periodontitis niche.

Case Report: Interstitial-intralesional laser therapy and laser-assisted new attachment procedure for the treatment of alveolar bone loss provoked by an aggressive pyogenic granuloma.

Background: A pyogenic granuloma (PG) is a common benign vascular lesion found in the oral cavity. The gold standard treatment of this lesion, comprising surgical excision and the elimination of etiological factors, cannot avoid tooth loss in the case of an aggressive pyogenic granuloma. Because of the prominent properties of 980 nm and 635 nm diode lasers in photocoagulation and photobiomodulation, we applied these wavelengths in the treatment of a large pyogenic granuloma with alveolar bone loss. Case presentation: Our objective was to use a combination of interstitial-intralesional laser therapy, photocoagulation and laser-assisted new attachment procedure (LANAP) to preserve the teeth and periodontal tissue in a case of an aggressive pyogenic granuloma. Results: The patient was a 13-year-old Thai male with a pyogenic granuloma involving the interdental papilla and lingual gingiva of the lower left first and second molars. The teeth were also displaced by the lesion. After treatment with three sessions of photocoagulation, three sessions of interstitial-intralesional laser therapy and two sessions of LANAP, the lesion was completely resolved. The periodontal status of the teeth was improved at the six-month follow-up. Conclusion: The combination of interstitial-intralesional laser therapy, photocoagulation and LANAP was able to treat an aggressive pyogenic granuloma with tooth preservation.

Unloading of occlusal force aggravates alveolar bone loss in periodontitis.

BACKGROUND AND OBJECTIVE: Periodontitis (PD), a chronic infectious inflammatory disease initiated by bacteria, is associated with several local contributing factors including occlusal trauma. Previous studies have found that the traumatic occlusal force could aggravate alveolar bone loss during PD. However, the effect of reduced occlusal force during PD remains unclear. This study aimed to explore the effect of occlusal force unloading on PD onset and progression and its underlying mechanism as an effort to provide restoration suggestions for PD patients with dentition defect in clinic. This study might also propose occlusal force unloading could be a new local contributing factor for PD. MATERIALS AND METHODS: C57BL/6 mice were used to establish a PD model by the ligation of 5-0 silk around the mandibular left first molar (PD group) and an unloading experiment model by the extraction of their left maxillary first molar (EX group). The THP-1-derived macrophages were used to verify in vivo results. RESULTS: Micro-CT scanning and H&E staining results consistently showed that PD + EX group experienced the most severe alveolar bone resorption as compared to PD group and control group. Further RNA-sequencing analysis suggested that occlusal force unloading significantly enhanced osteoclastic resorption, inhibited osteoblastic activity, and promotes M1 and M2 macrophages polarization. Immunofluorescence staining (IF) results showed that compared with the PD group, PD + EX group significantly increased the ratio of M1/M2 polarization. Similar results were observed by RT-qPCR and IF in vitro: removal of compressive force led to an increased ratio of M1/M2 polarization in LPS-stimulated THP-1-derived macrophages. CONCLUSIONS: Our study demonstrated that occlusal force unloading aggravates bone resorption by increasing the ratio of M1/M2 macrophages polarization during PD, suggesting a previously unknown local contributing factor for PD, and providing a novel insight for dentists to restore missing teeth as an effort to maintain remaining dentition.

Quantification of Osteoprotegerin Plasma Levels in Patients with Periodontitis.

OBJECTIVE: Periodontitis (POD) is an infectious process directed at the structures supporting the teeth. Destruction of alveolar bone is considered one of the main causes of tooth loss in humans and is mediated by the host immune response. Osteoprotegerin (OPG), a protein that inhibits bone resorption by binding to the RANK ligand (RANKL), prevents osteoclastic differentiation. The aim of the study was to determine the plasma levels of OPG in patients with POD. METHODS: a case-control study with forty-nine patients with POD and 49 healthy controls were included in the study. OPG levels were determined by an ELISA test in plasma samples. RESULTS: OPG values (1.6203 ng/mL) were higher in the POD group compared with control group (1.2824 ng/mL). Among the studied groups, we detected significant differences in age, glycosylated haemoglobin (HbA1C), and plasma concentration of OPG (p < 0.05). CONCLUSION: plasma OPG levels are associated with bone formation and destruction processes, suggesting that OPG acts in a protective manner.

Osteoporosis and periodontal diseases - An update on their association and mechanistic links.

Periodontitis and osteoporosis are prevalent inflammation-associated skeletal disorders that pose significant public health challenges to our aging population. Both periodontitis and osteoporosis are bone disorders closely associated with inflammation and aging. There has been consistent intrigue on whether a systemic skeletal disease such as osteoporosis will amplify the alveolar bone loss in periodontitis. A survey of the literature published in the past 25 years indicates that systemic low bone mineral density (BMD) is associated with alveolar bone loss, while recent evidence also suggests a correlation between clinical attachment loss and other parameters of periodontitis. Inflammation and its influence on bone remodeling play critical roles in the pathogenesis of both osteoporosis and periodontitis and could serve as the central mechanistic link between these disorders. Enhanced cytokine production and elevated inflammatory response exacerbate osteoclastic bone resorption while inhibiting osteoblastic bone formation, resulting in a net bone loss. With aging, accumulation of oxidative stress and cellular senescence drive the progression of osteoporosis and exacerbation of periodontitis. Vitamin D deficiency and smoking are shared risk factors and may mediate the connection between osteoporosis and periodontitis, through increasing oxidative stress and impairing host response to inflammation. With the connection between systemic and localized bone loss in mind, routine dental exams and intraoral radiographs may serve as a low-cost screening tool for low systemic BMD and increased fracture risk. Conversely, patients with fracture risk beyond the intervention threshold are at greater risk for developing severe periodontitis and undergo tooth loss. Various Food and Drug Administration-approved therapies for osteoporosis have shown promising results for treating periodontitis. Understanding the molecular mechanisms underlying their connection sheds light on potential therapeutic strategies that may facilitate co-management of systemic and localized bone loss.

Study on the role of pyroptosis in bone resorption induced by occlusal trauma with or without periodontitis.

BACKGROUND AND OBJECTIVE: Occlusal trauma is considered to be a contributing factor to bone loss associated with inflammatory periodontal disease. We hypothesized that pyroptosis, a recently discovered inflammation-induced programmed cell death pathway, plays a role in occlusal trauma. MATERIALS AND METHODS: The occlusal trauma model was established using a cemented 1-mm elevated computer-aided design and manufacturing (CAD/CAM) metal crown. The periodontitis model was established by periodontal wire ligation with lipopolysaccharide (LPS) injection. The rats were sacrificed at 1, 2, 3, and 4 weeks. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the expression of pyroptosis-, inflammation-, and osteoclast-related markers. Micro-computed tomography (micro-CT) was used to determine bone morphology parameters. Tissue morphology was evaluated using hematoxylin and eosin staining (H&E). Osteoclasts were identified using tartrate-resistant acid phosphatase (TRAP) staining. The expression and distribution of factors related to pyroptosis and inflammation were evaluated by immunohistochemistry (IHC). The colocalization of dead cells and cysteinyl aspartate-specific proteinase-1 (caspase-1)-positive cells was analyzed by immunofluorescence. RESULTS: Quantitative real-time polymerase chain reaction and IHC results showed that occlusal trauma induced the expression of pyroptotic factors during the early stages, while occlusal trauma with periodontitis upregulated the expression of pyroptotic factors at the later stages. The results of qRT-PCR, TRAP staining, and micro-CT showed that occlusal trauma with periodontitis increased the production of proinflammatory cytokines, leading to severe bone loss. Glyburide, an NOD-like receptor pyrin domain containing protein 3 (NLRP3)inhibitor, reduced the expression of pyroptosis markers induced by occlusal trauma with periodontitis and reversed bone resorption. CONCLUSIONS: Pyroptosis was involved in bone loss induced by occlusal trauma with or without periodontitis, while glyburide reversed inflammation and bone resorption.

Nociceptor Neurons Magnify Host Responses to Aggravate Periodontitis.

Periodontitis is a highly prevalent chronic inflammatory disease that progressively destroys the structures supporting teeth, leading to tooth loss. Periodontal tissue is innervated by abundant pain-sensing primary afferents expressing neuropeptides and transient receptor potential vanilloid 1 (TRPV1). However, the roles of nociceptive nerves in periodontitis and bone destruction are controversial. The placement of ligature around the maxillary second molar or the oral inoculation of pathogenic bacteria induced alveolar bone destruction in mice. Chemical ablation of nociceptive neurons in the trigeminal ganglia achieved by intraganglionic injection of resiniferatoxin decreased bone loss in mouse models of experimental periodontitis. Consistently, ablation of nociceptive neurons decreased the number of osteoclasts in alveolar bone under periodontitis. The roles of nociceptors were also determined by the functional inhibition of TRPV1-expressing trigeminal afferents using an inhibitory designer receptor exclusively activated by designer drugs (DREADD) receptor. Noninvasive chemogenetic functional silencing of TRPV1-expressing trigeminal afferents not only decreased induction but also reduced the progression of bone loss in periodontitis. The infiltration of leukocytes and neutrophils to the periodontium increased at the site of ligature, which was accompanied by increased amount of proinflammatory cytokines, such as receptor activator of nuclear factor κΒ ligand, tumor necrosis factor, and interleukin 1ß. The extents of increase in immune cell infiltration and cytokines were significantly lower in mice with nociceptor ablation. In contrast, the ablation of nociceptors did not alter the periodontal microbiome under the conditions of control and periodontitis. Altogether, these results indicate that TRPV1-expressing afferents increase bone destruction in periodontitis by promoting hyperactive host responses in the periodontium. We suggest that specific targeting of neuroimmune and neuroskeletal regulation can offer promising therapeutic targets for periodontitis supplementing conventional treatments.

Distribution of neutrophil and monocyte/macrophage populations induced by the CXCR4 inhibitor AMD3100 in blood and periodontal tissue early after periodontitis induction.

CXCR4, a CXCL12 receptor, is expressed on epithelial cells, fibroblasts, and inflammatory cells. The CXCR4-CXCL12 interaction is related to the migration of neutrophils and monocytes/macrophages. Periodontitis, an inflammatory disease mainly caused by gram-negative bacteria, is characterized by infiltration of circulating inflammatory cells and alveolar bone (AB) loss. To investigate whether CXCR4 is involved in the distribution of neutrophils and monocytes/macrophages early after periodontitis induction, we examined the effects of AMD3100 (AMD), a CXCR4 antagonist, in ligature-induced periodontitis mice and LPS-injected air pouch mice. The periodontitis study was accomplished in control (C), periodontitis (P), and P + AMD groups. Periodontitis was induced by ligation of the mandibular first molar. AMD was intraperitoneally administered daily beginning the day before ligation until sacrifice on the third day after ligation. The air pouch study was accomplished in C, lipopolysaccharide (LPS), and LPS + AMD groups. Air pouches on mice backs were formed by subcutaneous injection of sterilized air. AMD was administered and then LPS was injected into the air pouch. For the detection of neutrophils and monocytes/macrophages in blood and air pouch exudates, flow cytometry was performed with anti-Ly6G/anti-CD11b antibodies (Abs) and anti-CD115 Ab, respectively. In periodontal tissue, Ly6G+ cells and CD115+ cells were counted by immunohistological analysis. AB loss was estimated by the periodontal ligament area in the furcation. In the periodontitis study, the P group showed higher numbers of Ly6G+ cells and CD115+ cells in blood and periodontal tissue than the C group. The P + AMD group showed a greater number of Ly6G+ cells and CD115+ cells in blood, but not in periodontal tissue compared to the P group. There was no difference in AB loss between the P and P + AMD groups. In the air pouch study, the LPS group had higher levels of Ly6G+ CD11b+ cells and CD115+ cells in both blood and exudates than the C group. The number of these cells in the LPS + AMD group was higher in blood than in the LPS group, but not in the exudates. The CXCR4 antagonist further increased neutrophil and monocyte/macrophage populations in the blood, but did not alter the levels in the periodontal tissue and exudates in mice with periodontitis and LPS-injected air pouches. These results suggest that during inflammatory conditions such as periodontitis, CXCR4 is involved in the distribution of neutrophils and monocytes/macrophages in the blood, but not in inflamed peripheral tissues.

Suppression of alveolar bone resorption by salubrinal in a mouse model of periodontal disease.

AIMS: The relationship between stress to endoplasmic reticulum (ER) and periodontitis has been known, and ER stress induced by Porphyromonas gingivalis results in the loss of alveolar bone. Salubrinal is a small synthetic compound and attenuates ER stress through inhibition of de-phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). In this study, we examined whether salubrinal attenuates periodontitis in a mouse model of experimental periodontal disease. MATERIALS AND METHODS: We evaluated loss of alveolar bone and attachment levels in periodontium using micro-computed tomography (µCT) and hematoxylin-eosin (HE) staining, respectively. Furthermore, we measured osteoclast numbers using tartrate-resistant acid phosphatase (TRAP) staining and osteoblast numbers using HE staining for bone resorption and for bone formation, respectively. To examine the inhibitory effects of salubrinal against pro-inflammatory cytokines, we measured TNF-α and IL1-ß score in periodontium using immunohistostaining. KEY FINDINGS: The results revealed that salubrinal suppressed loss of alveolar bone and attachment levels in periodontium induced by periodontitis. It decreased osteoclast numbers and increased osteoblasts. It also suppressed the expression levels of TNF-α in periodontium. SIGNIFICANCE: These results show that salubrinal alleviates periodontitis through suppression of alveolar bone resorption and the pro-inflammatory cytokine, and promotion of the bone formation. Since salubrinal has been shown to have these beneficial effects for periodontal disease, it may provide a novel therapeutic possibility for the disease.

The Effect of Controlled Diabetes and Hyperglycemia on Implant Placement with Simultaneous Horizontal Guided Bone Regeneration: A Clinical Retrospective Analysis.

Diabetes represents a challenge in implant therapy because hyperglycemia may negatively affect bone regeneration, directly compromising clinical outcomes and increasing clinical failures. The aim of this retrospective study is to analyse the prognostic significance of HbA1c levels in patients undergoing implant placement associated with horizontal guided bone regeneration. Thirty-four patients were divided into 3 groups according to their HbA1c levels: nondiabetic normoglycemic patients (HbA1c < 5.7%), nondiabetic hyperglycemic patients (HbA1c < 6.5%), and controlled diabetic patients (HbA1c < 7%). Primary outcomes were dimensional changes in height (VDH) and width (DW) of the peri-implant defect. Secondary outcomes were evaluations of periodontal parameters of adjacent tooth sites, wound healing, marginal bone loss (MBL), and survival and success rates. At T 1 (6 months), mean VDH values in groups 1, 2, and 3 were, respectively, 0.07, 0.5, and 0.25 mm. Mean DW values in those same groups were, respectively, 0.07, 0.38, and 0.33 mm. HbA1c levels were not statistically related to VDH and DW values at T 1. No statistically significant differences were observed in MBL between groups (p = 0.230). Implant survival and success rates were, respectively, 98% and 96%. Simultaneous guided bone regeneration is a feasible procedure for the treatment of horizontal bone deficiencies in controlled diabetic patients.

Atrofia combinada maxilo-mandibular. Uso de implantes cortos y estrechos (BTI(R) CORE y BTI(R) 3.0) / Combined maxillo-mandibular atrophy. Use of short and narrow implants (BTI(R) CORE AND BTI(R) 3.0)

Cada día con más frecuencia en las clínicas odontológicas nos enfrentamos a atrofias maxilares y mandibulares más extremas y en muchos casos con el retratamiento de implantes fracasados biológica y/o mecánicamente. En el presente caso clínico mostramos una paciente con una atrofia combinada (horizontal y verticalmente) además de un tratamiento con implantes dentales fracasado

More and more frequently in dental clinics we are confronted with more extreme maxillary and mandibular atrophy and in many cases with the retreatment of biologically and/or mechanically failed implants. In the present clinical case we show a patient with a combined atrophy (horizontally and vertically) in addition to a failed dental implant treatment

A influência da sobre carga vertical em diferentes níveis ósseos em implantes unitários: estudo comparativo de dois sistemas de implantes / The influence of vertical load on different bone levels in single implants: a comparative study of two implant systems

Embora existe um alto índice de sucesso implantes dentários, podem ocorrer perda da osseintegração após instalação das próteses sobre implante e as causas são as periimplantites e sobre cargas oclusais. Diferentes conexõessurgiram para o melhor desempenho estético, biomecânico e para evitar perdas ósseas perimplantares. Para analisar às deformações geradas ao redor dos implantes e suas conexões, as duas metodologias utilizadas neste estudo e que apresentam resultados numéricos,foram a análise de elementos finitos e a extensometria linear.Para o teste do FEA, foi utilizado o software Rhinoceros 4.0 para obter os desenhos em 3D dos dois modelos de implantes,com o mesmo comprimento e largura, um hexágono externo HE (Titaoss® TM cortical Intraoss®, SP, Brasil) com diâmetro de 3,75 mm e comprimento de 13 mm e o segundo sendo um implante conexão interna (CM) (Titaoss® Max Cone Morse, Intraoss®, SP, Brasil). Sobre os implantes foram modelados seus abutments respectivamente, Ucla anti- rotacional com plataforma de 4.1 mm e um Pilar Cone Morse CMN com transmucoso de 0,8 mm. Ambos abutments para próteses parafusadas e foram exportados para o software de análise (ANSYS 17.0, ANSYS Inc., Houston, TX, USA) em formato STEP.Para o teste de extensometria, foram obtidos blocos de poliuretano (Poliuretano F160 ISO Axson, Cercy, França) de forma retangular com dimensões internas de 95 x 45 x 30 mm e intalados implantes Titaoss® Max Cone Morse 3,75 X 13 mm e os implantes Titaoss® TM 3,75 X 13 mm (Intraoss- SP - Brasil), e os abutments e coroas metálicas de cromo-cobalto. Formado 4 grupos: a) CM no; b) HE no, c) CM po e d) He po; em cada grupo foram instalados 4 extensômetros tangenciando cada um dos implantes, segundo mapas colorimétricos da região de maior microdeformação óssea. Na aplicação de carga, foi utilizado o dispositivo de aplicação de carga-DAC(Nishioka - Proc. 08/53071-4), com carga axial de 30 kg aplicadas por um período de 10 segundos (Mericske-Stern et al.) na fosseta central (carga axial).Resultados:1) FEA- a) Tensão de von-Mises gerada no conjunto implante/parafuso mostrou maior concentraçao de tensao no parafuso protético de ambos os grupos independente da perda óssea; b) Tensão de von-Mises gerada na região mais estressada que mostrou a possível falha na região da cabeça do parafuso de ambos os grupos independente da perda óssea; c) Tensão de von-Mises gerada no implante em secçao longitudinal foi maior concentraçao de tensao na plataforma do hexagono externo, mas, com pouca diferença no restante do corpo do implante, e d) microdeformaçao gerada no interior do bloco de poliuretano .Não foi possível notar diferenças significativas entre as diferentes conexões. Para os implantes com perda óssea é possível notar maior deformaçao ápica. 2) Na extensometria foi realizada a média da deformação gerada de cada os quatro grupos, no qual não apresentou diferenças numéricas entre os grupos. Neste estudo podemos concluir que não há diferenças significativas na microdeformação entre o grupo dos implantes CM no e HE no, com uma maior deformação CM e HE quando há presença de perda óssea(AU)

Although there is a high success rate, dental implants may lose osseintegration after implantation of prostheses on implants and the causes are peri-implantitis and occlusal loads.Different connections have emerged for better aesthetic and biomechanical performance to prevent perimplant bone loss.To analyze the deformations generated around the implants and their connections, the two methodologies used in this study and which present numerical results were the analysis of finite elements and linear extensometry.The Rhinoceros 4.0 software was used to obtain the 3D drawings of the two implant models with the same length and width, an external hexagon HE (Titaoss® TM cortical Intraoss®, SP, Brazil) with a diameter of 3.75 mm and a length of 13 mm and the second being an internal connection (CM) implant (Titaoss® Max Cone Morse, Intraoss®, SP, Brazil). The abutments were modeled on the implants, respectively, Ucla anti-rotational with 4.1 mm platform and a Morse Cone Abutment CMN with 0.8 mm transmucous. Both abutments for screwed prostheses and were exported to the analysis software (ANSYS 17.0, ANSYS Inc., Houston, TX, USA) in STEP format.For the extensometry test, rectangular polyurethane blocks (Polyurethane F160 ISO Axson, Cercy, France) with internal dimensions of 95 x 45 x 30 mm and Titaoss® Max Cone Morse 3.75 X 13 mm implants and implants were obtained Titaoss® TM 3.75 X 13 mm (Intraoss-SP - Brazil), and the abutments and metallic crowns of chromium-cobalt. Forming 4 groups: a) CM no; b) HE no; c) CM po and d) He po, each group installed 4 strain gauges tangent to each of the implants, according to colorimetric maps of the region with the greatest bone microdeformation. In the load application, the DAC load application device (Nishioka- Proc. 08 / 53071-4) was used, with an axial load of 30 kg applied for a period of 10 seconds (Mericske-Stern et al.) In the pit central (axial load).Results: 1) FEA- a) von-Mises tension generated in the implant / screw set showed a higher concentration of tension in the prosthetic screw of both groups regardless of bone loss; b) von-Mises tension generated in the most stressed region, showing possible failure in the screw head region of both groups regardless of bone loss; c) VonMises stress generated in the implant in longitudinal section was higher stress concentration in the external hexagon platform but with little difference in the rest of the implant body, and d) microdeformation generated inside the polyurethane block, it was not possible to notice significant differences between the different connections. For implants with bone loss, it is possible to notice greater apical deformation. 2) In the extensometry, the average strain generated for each of the four groups was performed, in which there were no numerical differences between the groups. In this study we can conclude that there was no difference in microdeformation between the group of CM implants and HE no, with a greater CM and HE deformation when there is bone loss(AU)