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Background: Periodontitis and diabetes mellitus (DM) exhibit a bidirectional relationship and are globally significant systemic chronic conditions. The utilization of antibiotics alongside non-surgical periodontal treatment (NSPT) has been a subject of investigation in numerous clinical studies involving human subjects. Thus, the objective of this systematic review is to address the following question: "What is the efficacy of scaling and root planing (SRP) associated with antimicrobials in patients with type 2 DM and periodontitis?". Methods: A systematic review of the literature was conducted encompassing databases such as MEDLINE/PubMed, Scopus, and Web of Science up to July 2024. Additionally, alerts were configured to capture studies published from the initial search until manuscript submission. Randomized clinical trials assessing clinical periodontal parameters in DM patients undergoing SRP and receiving either topical or systemic antibiotics were compared against a control group (SRP only). Two investigators independently screened articles, extracted data, and evaluated their quality. The selection process, study characteristics, risk of bias, impact of antibiotics on clinical parameters, and certainty of evidence were elucidated in both textual and tabular formats. Meta-analysis was performed separately with forest plots generated for treatment modalities, period of evaluation, and type of antibiotics used. Results: Following the analysis of abstracts and full articles, a total of 30 randomized clinical trials were incorporated into this review, comprising 9 studies on the association of topical antibiotics and 21 studies on systemic antibiotic administration. The principal periodontal parameters assessed included probing pocket depth (PPD), clinical attachment level (CAL), plaque index (PI), and bleeding on probing (BoP). Conclusions: Analysis of the results led to the conclusion that adjunctive periodontal treatment with either topical or systemic antibiotics confers subtle clinical benefits. Nevertheless, owing to the heightened emergence of resistant bacteria and potential side effects, the use of antibiotic therapy in periodontal treatment should be judiciously administered.
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Contemporary dentistry has increased the demand for predictable functional and esthetic results in a short period of time without compromising the long-term success of rehabilitation. Recent advances in surgical techniques have provided alternatives that allow the prosthetic rehabilitation of complex implant-supported cases through minimally invasive techniques. In this context, immediate dentoalveolar restoration (IDR) was described aiming at restoring function and esthetics through the reconstruction of lost periodontal tissues followed by immediate implant placement in order to minimize treatment time and surgical morbidity in a one-stage approach. Therefore, the aim of this clinical case is to describe the reconstruction and rehabilitation of a hopeless tooth in the maxillary region in a one-stage approach by means of IDR. The proposed steps to rehabilitate the case involved atraumatic dental extraction, immediate implant placement, and hard tissue augmentation by means of cortical-medullary bone graft harvested from the maxillary tuberosity. Afterwards, a provisional restoration was manufactured and installed to the implant allowing immediate prosthesis provisionalization and function in the same operatory time. Six months after the surgical procedure, the final prosthesis was manufactured and installed. The follow-up of nine years demonstrated the preservation of hard and soft tissue without tissue alteration and a successful esthetic outcome. The surgical protocol used allowed the ideal three-dimensional placement of the implant with the restoration of the bone buccal wall, favoring the esthetic and functional outcome of the case with harmony between white and pink esthetics. In conclusion, the employed treatment validated immediate implant-supported restoration of the missing tooth with high predictability. Furthermore, this protocol resulted in fewer surgical interventions, regeneration, and preservation of peri-implant tissues reaching the patient's expectations.
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BACKGROUND AND OBJECTIVE: The resorption of alveolar ridge bone and maxillary sinus pneumatization are challenges to implant-supported prosthetic rehabilitation. Bone regeneration using bone substitutes and growth factors are alternatives for maxillary sinus augmentation (MSA). Therefore, we sought to evaluate the effects of the association between leukocyte and platelet-rich fibrin (L-PRF) and deproteinized bovine bone mineral (DBBM) in MSA procedures. MATERIALS AND METHODS: Thirty-six maxillary sinuses from 24 individuals were included in this randomized clinical trial. The maxillary sinuses were randomly grafted with LPRF and DBBM (test group) or grafted only with DBBM (positive control). Dental implants were installed in the test group following two periods of evaluation: after 4 (DBBM+LPRF4) and 8 (DBBM+LPFR8) months of sinus graft healing, while the control group received implants only after 8 months. Cone beam computed tomography (CBCT) was taken 1 week after surgery (T1) and before implant placement (T2). Bone samples were collected during implant placement for histomorphometric and immunohistochemical (IHC) analysis. The primary implant stability was assessed by resonance frequency analysis. RESULTS: CBCT analysis demonstrated a significant decrease in bone volume from T1 to T2 in all groups without differences among them. Histologically, the test group showed significantly increase in bone neoformation in both periods of evaluation (LPRF+DBBM4: 44.70±14.01%; LPRF+DBBM8: 46.56±12.25%) compared to the control group (32.34±9.49%). The control group showed the highest percentage of residual graft. IHC analysis showed increased staining intensity of osteocalcin (OCN), vascular endothelial growth factor (VEGF), and runt related transcription factor 2 (RUNX-2) in LPRF+DBBM4 group, and osteopontin (OPN) in the L-PRF+DBBM8. Primary implant stability was successfully achieved (above 60 in implant stability quotient) in all the evaluated groups. CONCLUSION: Combination of L-PRF and DBBM increased and accelerated new bone formation allowing early implant placement probably due to the higher protein expression of RUNX2, VEGF, OCN, and OPN. These data suggest that the use of L-PRF might be an interesting alternative to use in combination with DBBM for augment the maxillary sinuses allowing the installation of appropriate length implants in shorter period of time. CLINICAL RELEVANCE: This study showed improvement in bone neoformation and accelerated healing when associating L-PRF and DBBM for maxillary sinus augmentation procedures. TRIAL REGISTRATION: This study was registered before participant recruitment in Brazilian Registry of Clinical Trials (ReBEC - RBR-95m73t).
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Substitutos Ósseos , Fibrina Rica em Plaquetas , Levantamento do Assoalho do Seio Maxilar , Humanos , Animais , Bovinos , Seio Maxilar/cirurgia , Seio Maxilar/patologia , Levantamento do Assoalho do Seio Maxilar/métodos , Fator A de Crescimento do Endotélio Vascular/farmacologia , Osteogênese , Transplante Ósseo/métodos , Implantação Dentária Endóssea , Substitutos Ósseos/farmacologia , LeucócitosRESUMO
Recent evidence suggests an association between hypertension and periodontitis, although the pathways and implications underlying both chronic conditions are still poorly understood. Therefore, the aim of this study was to evaluate the relationship between hypertension and periodontitis through an observational clinical study using periodontal, physical, and biochemical analyses in hypertensive and non-hypertensive individuals with periodontitis. A total of one hundred patients were divided into two groups. The first group was hypertensive patients with periodontitis. The second group was non-hypertensive patients with periodontitis. Periodontal parameters of probing depth, bleeding on probing, and clinical attachment level were evaluated. The systolic, diastolic, mean, and differential blood pressure were measured in the physical examination. In addition, body mass index and waist-hip ratio were verified. Biochemical tests for glycated hemoglobin, fasting blood glucose, estimated blood glucose, total cholesterol, high-density lipoprotein, creatinine, glutamate pyruvate transaminase, glutamic oxaloacetic transaminase, and C-reactive protein were evaluated. The data were submitted for statistical analysis (α = 0.05%). The results of this study demonstrated that patients with cardiovascular disease did not present with worse periodontal clinical parameters in the conditions studied. However, it is important to bear in mind that this cross-sectional study has some inherent limitations to its design; therefore, to study the relationship between hypertension and periodontitis further, an interventional randomized clinical trial should be conducted.
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We sought to evaluate the effects of non-surgical periodontal treatment (NSPT) on periodontal clinical parameters, systemic blood pressure (BP), and plasma levels of systemic inflammation markers in patients with combined refractory arterial hypertension (RAH) and stage III grade B periodontitis. Twenty-seven participants with RAH and periodontitis received NSPT. The analyzed clinical parameters were probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque index (PI). An assessment was performed for systemic BP, complete blood count, coagulogram, creatinine measurement, C-reactive protein (CRP), glycated hemoglobin, cholesterol, glutamic oxaloacetic transaminase, glutamate pyruvic transaminase, waist-hip ratio, and body mass index. In the follow-up period, twenty-two patients were evaluated at baseline and after 90 and 180 days. The data were submitted for statistical analysis (α = 0.05%). As expected, the clinical results showed a significant improvement in the percentages of PI, BOP, PD, and CAL, which were statistically significant at 90 and 180 days (p < 0.0001). Importantly, NSPT significantly reduced the blood level of CRP (p < 0.02). However, no significant reduction in BP parameters was noted in the evaluated follow-up periods. NSPT, despite the benefits in periodontal clinical parameters, reduced the plasma level of CRP but not the BP in patients with combined RAH and periodontitis.
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OBJECTIVE: To investigate the effect of voluntary physical activity (VPA) on inflammatory profile and the progression of experimental periodontal disease (PD) in mice. METHODS: Male C57BL/6 mice were randomly distributed into Control; VPA; PD and PD/VPA groups. We registered VPA (total volume of revolutions) and average speed (revolutions/minute) in a free running wheel for 30 days. On the 15th day, animals from the PD and PD/VPA groups received ligatures on the upper second molars bilaterally. On the 30th day animals were euthanized, and PD progression was assessed by measuring alveolar bone loss (ABL - the linear distance between the cemento-enamel junction and the alveolar bone crest on the teeth buccal surface). Gene expression of RANKL (kappa nuclear factor B receptor) OPG (osteoprotegerin), IL-1ß (interleukin 1 beta), IL-6 (interleukin 6) and TNF-α (tumor necrosis factor alpha) were evaluated by real-time PCR (quantitative Polymerase Chain Reaction - relative gene expression). RESULTS: The total volume of physical activity and the activity speed decreased along the seven days after ligature-placement (p < 0.05), returning to a similar pattern in relation to VPA group. Ligature placement produced significant bone resorption, and increased RANKL, IL-1ß, IL-6 and TNF-α expression. VPA reduced ABL (p < 0,05) and the expression of TNF-α and IL-1ß, whereas increased OPG expression. CONCLUSION: Animals induced to PD with access to the VPA wheel presented both lower gingival inflammation and less alveolar bone resorption in comparison to animals without access to the wheel.
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Perda do Osso Alveolar , Periodontite , Perda do Osso Alveolar/patologia , Animais , Interleucina-6 , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoprotegerina/metabolismo , Periodontite/metabolismo , Ligante RANK/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Periodontitis, a highly prevalent multicausal chronic inflammatory and destructive disease, develops as a result of complex host-parasite interactions. Dysbiotic bacterial biofilm in contact with the gingival tissues initiates a cascade of inflammatory events, mediated and modulated by the host's immune response, which is characterized by increased expression of several inflammatory mediators such as cytokines and chemokines in the connective tissue. If periodontal disease (PD) is left untreated, it results in the destruction of the supporting tissues around the teeth, including periodontal ligament, cementum, and alveolar bone, which lead to a wide range of disabilities and poor quality of life, thus imposing significant burdens. This process depends on the differentiation and activity of osteoclasts, the cells responsible for reabsorbing the bone tissue. Therefore, the inhibition of differentiation or activity of these cells is a promising strategy for controlling bone resorption. Several pharmacological drugs that target osteoclasts and inflammatory cells with immunomodulatory and anti-inflammatory effects, such as bisphosphonates, anti-RANK-L antibody, strontium ranelate, cathepsin inhibitors, curcumin, flavonoids, specialized proresolving mediators, and probiotics, were already described to manage inflammatory bone resorption during experimental PD progression in preclinical studies. Meantime, a growing number of studies have described the beneficial effects of herbal products in inhibiting bone resorption in experimental PD. Therefore, this review summarizes the role of several pharmacological drugs used for PD prevention and treatment and highlights the targeted action of all those drugs with antiresorptive properties. In addition, our review provides a timely and critical appraisal for the scientific rationale use of the antiresorptive and immunomodulatory medications in preclinical studies, which will help to understand the basis for its clinical application.
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Perda do Osso Alveolar , Reabsorção Óssea , Doenças Periodontais , Periodontite , Perda do Osso Alveolar/prevenção & controle , Reabsorção Óssea/complicações , Reabsorção Óssea/tratamento farmacológico , Humanos , Osteoclastos/metabolismo , Doenças Periodontais/complicações , Doenças Periodontais/tratamento farmacológico , Periodontite/complicações , Qualidade de VidaRESUMO
BACKGROUND AND OBJECTIVES: Many studies have been conducted to better understand the molecular mechanism involved with periodontitis progression. There has been growing interest in the potential impact of obesity on periodontitis onset and progression, but the mechanisms involved remain to be elucidated. The present study was designed to determine the impact of obesity on experimentally induced periodontitis in rats and identify novel pathways involved. METHODS: Sixteen Holtzman rats were distributed into two groups (n = 8): ligature-induced periodontitis (P) and obesity plus ligature-induced periodontitis (OP). Obesity was induced by a high-fat diet for 70 days, whereas periodontitis was induced for 20 days, with a cotton thread placed around the upper first molars bilaterally. Alveolar bone loss was measured by microtomographic analysis and histologically by histometry on the hemimaxillae. The protein composition of the periodontal ligament was evaluated by proteomic analysis. RESULTS: Data analysis (body weight, adipose tissue weight, and blood test) confirmed obesity induction, whereas bone loss was confirmed by micro-CT and histologic analyses. Proteome analysis from the periodontal ligament tissues (PDL) identified 819 proteins, 53 exclusive to the P group, 28 exclusive to the OP group, and 738 commonly expressed. Validation was performed by immunohistochemistry for selected proteins (spondin1, vinculin, and TRAP). CONCLUSION: Histologically, it was found that obesity did not significantly affect bone loss resulting from periodontitis. However, the present study's findings indicated that obesity affects the proteome of PDL submitted to experimental periodontitis, allowing for identifying potential targets for personalized approaches.
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Perda do Osso Alveolar , Periodontite , Perda do Osso Alveolar/patologia , Animais , Obesidade/complicações , Ligamento Periodontal/metabolismo , Periodontite/metabolismo , Proteoma , Proteômica , Ratos , Ratos WistarRESUMO
Rehabilitation of atrophic maxilla with dental implants is still a challenge in clinical practice especially in cases of alveolar bone resorption due to peri-implantitis and pneumatization of the maxillary sinuses. Several surgical approaches have been employed to reconstruct the lost tissues allowing the proper tridimensional position of the implants. In this context, the aim of this case report is to describe a surgical and prosthetic approach to fully rehabilitate the atrophic maxilla with dental implants. The patient presented with unsatisfactory functional and esthetical implant-supported prosthesis with some of the implants already lost by peri-implantitis. The remaining three implants were also affected by peri-implantitis. Reversal prosthetic planning was performed, and a provisional prosthesis was fabricated and anchored in two short implants. Sinus floor augmentation procedure and onlay bone graft were then accomplished. After a healing period of 8 months, digital-guided surgery approach was performed to place the implants. Finally, a definitive prosthesis was installed. One-year follow-up has revealed stabilization of the bone tissue level, successful osseointegration, and a pleasant esthetic and functional result. A proper diagnosis and careful planning play an important role to enhance precision and to achieve patient esthetic and functional outcomes.
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INTRODUCTION: Orthodontic movement triggers a sequence of cellular and molecular events that may be affected by different systemic conditions. This study evaluated the effect of obesity on rat periodontal tissue remodeling induced by mechanical orthodontic force. METHODS: Thirty-two Holtzman rats were distributed into 4 groups: control, obesity induction (O), orthodontic movement (M), and obesity induction and orthodontic movement (OM). Obesity was induced by a high-fat diet for 90 days. After 15 days of orthodontic movement, the animals were killed. Obesity induction was confirmed by animal body weight, adipose tissue weight, and serologic analysis. Periodontal tissue remodeling was evaluated using microcomputed tomography and histologic analysis. The gene expression of adipokines and cytokines in gingival tissues was evaluated. RESULTS: An increase in body and adipose tissue weight was observed in the obesity induction groups. The O group presented an increase in lipids and blood glucose. The OM group showed a decrease in bone volume fraction and bone mineral density compared with all other groups and a tendency for more rapid tooth movement than the M group. The OM group showed a higher quantity of inflammatory cells and higher Mmp1 expression than the O group. The O and OM groups showed higher Nampt expression than the control group and lower Nampt expression than the M group. CONCLUSIONS: Obesity modulates periodontal tissue remodeling during orthodontic movement and results in more inflammation and bone loss than in nonobese animals.
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Obesidade , Técnicas de Movimentação Dentária , Animais , Remodelação Óssea , Gengiva , Ligamento Periodontal , Ratos , Ratos Sprague-Dawley , Microtomografia por Raio-XRESUMO
OBJECTIVE: The aim of this study was to investigate the effects of the long-term alendronate administration on bone healing in defects created in rat calvarias. MATERIALS AND METHODS: Female Wistar rats were randomly distributed into 2 groups: Control (CTL): animals received saline solution once a week; and Alendronate (ALD): rats underwent alendronate treatment (1 mg/kg/weekly). After 120 days from the commencement of treatment, a critical size defect was created in all animals, and 10 animals from each group were sacrificed at 5, 10, 15, 20, 25, 30, 45 and 60-days after the defect creation. On the day of sacrifice, urine and blood samples were collected for determination of the serum levels of bone resorption and formation markers by enzyme linked immunosorbent assay, and the urinary concentration of deoxypyridinoline. Bone mineral density (BMD) in the femurs, descriptive histology, tartrate-resistant acid-phosphatase staining and immunohistochemical analyzes were assessed in the calvaria. RESULTS: Alendronate group showed increased BMD compared to the test group. The concentration of C-terminal telopeptide of type I collagen and deoxypyridinoline decreased significantly, and the concentration of aminoterminal propeptide of procollagen type 1 and osteocalcin were significant lower in the alendronate group. Immunohistochemical analysis showed significant downregulation in the inducible nitric oxide synthase, runt-related transcription factor-2, cathepsin-K and receptor activator of nuclear factor kappa-B ligand expression in the alendronate group. Vascular endothelial growth factor and osteopontin were upregulated in the later periods of alendronate group. CONCLUSIONS: Our results suggest that long-term treatment with alendronate did not compromise the repair processing of critical size defects in rat.
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Alendronato , Regeneração Óssea/efeitos dos fármacos , Crânio/efeitos dos fármacos , Alendronato/farmacologia , Animais , Densidade Óssea , Feminino , Osteopontina , Ratos , Ratos Wistar , Crânio/patologia , Fator A de Crescimento do Endotélio VascularRESUMO
OBJECTIVE: The aim of this study was to compare the periodontal tissue changes resulting from different methods of orthodontic tooth extrusion in dogs. MATERIALS AND METHODS: Notches were surgically prepared in the root surface at the bone crest level of the first premolars of mongrel dogs. After 37 days, extrusion of the first lower and upper premolars was randomly performed by 3 different methods: conventional orthodontic extrusion (OE); open flap debridement performed immediately before orthodontic extrusion (OF); and orthodontic extrusion associated with weekly fiberotomy and scaling (FS). For all groups, extrusion was performed for 21 days followed by one-month retention and sacrifice. Periodontal parameters, descriptive histology, and histomorphometric analyses were performed at the end of the experimental period. RESULTS: The median extrusion was 2.25 in the fiberotomy group, 2.0 mm in the open flap group and 1.0 mm in the orthodontic extrusion group with no significant differences between groups. The highest distance between reference notch and bone crest was observed in the fiberotomy group (p < 0.05). Histologically, radicular resorption repaired with cellular cementum was detected in all groups. CONCLUSIONS: Tooth extrusion was successfully achieved with all of the different methods of orthodontic tooth extrusion with no statistical significance between techniques. The fiberotomy approach was effective in avoiding coronal displacement of periodontal tissues. Fiberotomy associated with scaling should be indicated if the objective of the treatment is extrusion without periodontal tissue displacement.
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Extrusão Ortodôntica , Reabsorção da Raiz , Animais , Cemento Dentário , Cães , Periodonto , Técnicas de Movimentação DentáriaRESUMO
Previous studies have shown that topical application of lectin Artin-M accelerates wound healing in the rat oral mucosa. The aim of this study was to evaluate, by means of histology and immunohistochemistry (IHC) the effects of Artin-M on wound healing in the palatal mucosa in dogs. Three full thickness wounds of 6 mm diameter were surgically created in the palatal mucosa of twenty dogs and randomly divided into three groups according to one of the treatment assigned: Group C-Control (coagulum); Group A-Artin-M gel; Group V-Vehicle (carboxymethylcellulose 3%). Each animal received all the three experimental treatments. Afterwards, four animals were killed at 2, 4, 7, 14 and 21 days post-surgery. Wounded areas were photographed and scored for macroscopic evaluation. Biopsies were harvested and used for descriptive histological analysis, proliferating cell nuclear antigen IHC and measurement of myeloperoxidase activity. The results demonstrated faster wound closure in group A in comparison to the other groups in all the periods evaluated. Histological analyses exhibited improved re-epithelialization and collagen fiber formation resulting in faster maturation of granulation tissue in group A compared to the other groups by day 14. Treatment with Artin-M gel significantly induced cell proliferation and increased volumetric density of fibroblasts at day 2 and 4 (p < 0.05). Neutrophil infiltration in group A was significantly higher than the other groups (p < 0.05) at the same time points. Collectively, our findings demonstrated that Artin-M may potentially favor wound healing on palatal mucosa lesions via recruitment of neutrophils and promotion of cell proliferation.
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Palato , Cicatrização , Animais , Cães , Fibroblastos , Lectinas , Mucosa Bucal , RatosRESUMO
Lipoproteins are important bacterial immunostimulating molecules capable of inducing receptor activator of nuclear factor-κB (RANKL) and osteoclast formation in vitro and in vivo . Although these molecules are present in periodontopathogenic bacteria, their role in periodontitis is not known. In this study, we used Pam2CSK4 (PAM2), a synthetic molecule that mimics bacterial lipoprotein, to investigate the effects of lipoproteins on periodontitis in mice. C57BL/6 male mice were randomly divided into three experimental groups: 1) Negative control group: animals received vehicle injection; 2) Positive control group: animals received injection of Escherichia coli lipopolysaccharide (LPS); 3) PAM2 group: animals received PAM2 injection. All the injections were performed bilaterally every other day into the palatal mucosa between first and second molars. After twenty-four days, the animals were euthanized to assess alveolar bone volume (micro-CT), cellular and extracellular composition in the gingiva (stereometric analysis), and osteoclast numbers (TRAP staining). Treatment with either PAM2 or LPS induced gingival inflammation, as demonstrated by increased infiltration of inflammatory cells and enhanced angiogenesis, associated with a smaller number of fibroblasts and decreased extracellular matrix. Importantly, treatment not only with LPS but also with PAM2 resulted in a larger number of TRAP+ multinucleated osteoclasts and significant loss of alveolar bone. Collectively, our data demonstrate that PAM2 can induce gingival inflammation and bone loss in mice, broadening the avenues of investigation into the role of lipoproteins in the pathogenesis of periodontal disease.
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Lipopeptídeos/farmacologia , Periodontite/etiologia , Periodontite/patologia , Receptor 2 Toll-Like/antagonistas & inibidores , Perda do Osso Alveolar/etiologia , Perda do Osso Alveolar/patologia , Processo Alveolar/efeitos dos fármacos , Processo Alveolar/patologia , Animais , Modelos Animais de Doenças , Gengiva/efeitos dos fármacos , Gengiva/patologia , Gengivite/etiologia , Gengivite/patologia , Masculino , Camundongos Endogâmicos C57BL , Osteoclastos/efeitos dos fármacos , Osteoclastos/fisiologia , Periodontite/microbiologia , Distribuição Aleatória , Fosfatase Ácida Resistente a Tartarato , Fatores de Tempo , Microtomografia por Raio-XRESUMO
We sought to evaluate the effects of magnesium (Mg) intake deficiency on bone metabolism in rats with induced periodontal disease (PD). Holtzman rats were randomly divided into two groups: Control - animals fed a standard diet and test - animals fed a diet with 90% Mg deficiency. After 60 days on the diets, all animals received ligature on the lower left first molars to induce PD. Animals were euthanized after 30 days following ligature placement. Blood and urine were collected for determination of serum concentrations of Mg, calcium, osteocalcin (OCN), alkaline phosphatase and parathyroid hormone (PTH) by enzyme-linked immunosorbent assay, and the urinary concentration of deoxypyridinoline (DPD). Systemic bone mineral density (BMD), bone volume and architectural bone parameters were evaluated by micro-CT in L4 lumbar vertebrae and mandible. Tartrate-resistant acid phosphatase staining and immunohistochemical (IHC) analysis of inducible nitric oxide synthase (iNOS), Runt-related transcription factor 2 (RUNX2), CD86, CD80, proliferating cell nuclear antigen, vascular endothelial growth factor, OCN and osteopontin were investigated. Reverse-transcription polymerase chain reaction was employed to assess mRNA expression of receptor-activator of nuclear factor-kB ligand, osteoprotegerin (OPG) and interleukin (IL)-6. Mg deficiency was associated with higher concentrations of PTH and DPD, and significant decrease on both systemic and mandibular BMD, as well as greater severity of alveolar and trabecular bone loss. Significant increase in osteoclasts was observed in the test group with PD. IHC analysis showed significant increase in the expression of iNOS and decreased expression of OCN and RUNX2. Increased IL-6 mRNA and decreased OPG mRNA expressions were evidenced in the test group with PD. Mg deficiency caused systemic effects indicative of altered bone metabolism in the vertebrae and affected both immune and stromal cells, aggravating inflammatory bone resorption in the ligature-induced model of periodontitis.
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Densidade Óssea , Reabsorção Óssea , Inflamação/metabolismo , Deficiência de Magnésio/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Biomarcadores/metabolismo , Cálcio/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Interleucina-6/metabolismo , Magnésio/metabolismo , Osteocalcina/metabolismo , Osteoclastos/metabolismo , Hormônio Paratireóideo/metabolismo , Periodontite/metabolismo , RNA Mensageiro/metabolismo , Ratos , Microtomografia por Raio-XRESUMO
Abstract Lipoproteins are important bacterial immunostimulating molecules capable of inducing receptor activator of nuclear factor-κB (RANKL) and osteoclast formation in vitro and in vivo . Although these molecules are present in periodontopathogenic bacteria, their role in periodontitis is not known. In this study, we used Pam2CSK4 (PAM2), a synthetic molecule that mimics bacterial lipoprotein, to investigate the effects of lipoproteins on periodontitis in mice. C57BL/6 male mice were randomly divided into three experimental groups: 1) Negative control group: animals received vehicle injection; 2) Positive control group: animals received injection of Escherichia coli lipopolysaccharide (LPS); 3) PAM2 group: animals received PAM2 injection. All the injections were performed bilaterally every other day into the palatal mucosa between first and second molars. After twenty-four days, the animals were euthanized to assess alveolar bone volume (micro-CT), cellular and extracellular composition in the gingiva (stereometric analysis), and osteoclast numbers (TRAP staining). Treatment with either PAM2 or LPS induced gingival inflammation, as demonstrated by increased infiltration of inflammatory cells and enhanced angiogenesis, associated with a smaller number of fibroblasts and decreased extracellular matrix. Importantly, treatment not only with LPS but also with PAM2 resulted in a larger number of TRAP+ multinucleated osteoclasts and significant loss of alveolar bone. Collectively, our data demonstrate that PAM2 can induce gingival inflammation and bone loss in mice, broadening the avenues of investigation into the role of lipoproteins in the pathogenesis of periodontal disease.
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Animais , Masculino , Periodontite/etiologia , Periodontite/patologia , Receptor 2 Toll-Like/antagonistas & inibidores , Lipopeptídeos/farmacologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/fisiologia , Periodontite/microbiologia , Fatores de Tempo , Distribuição Aleatória , Perda do Osso Alveolar/etiologia , Perda do Osso Alveolar/patologia , Modelos Animais de Doenças , Microtomografia por Raio-X , Processo Alveolar/efeitos dos fármacos , Processo Alveolar/patologia , Fosfatase Ácida Resistente a Tartarato , Gengiva/efeitos dos fármacos , Gengiva/patologia , Gengivite/etiologia , Gengivite/patologia , Camundongos Endogâmicos C57BLRESUMO
Specialized proresolving mediators (SPRM), which arise from n-3 long-chain polyunsaturated fatty acids (n-3FA), promote resolution of inflammation and may help to prevent progression of an acute inflammatory response into chronic inflammation in patients with arthritis. Thus, this study is aimed at determining whether systemic RvE1 treatment reduces arthritis onset and severity in murine collagen-induced arthritis (CIA) and spontaneous cytokine production by human rheumatoid arthritis (RA) synovial explants. 10-week-old DBA1/J male mice were subjected to CIA and treated systemically with 0.1 µg RvE1, 1 µg RvE1, 5 mg/kg anti-TNF (positive control group), PBS (negative control group), or with a combination of 1 µg of RvE1 plus 5 mg/kg anti-TNF using prophylactic or therapeutic strategies. After CIA immunization, mice were treated twice a week by RvE1 or anti-TNF for 10 days. Arthritis development was assessed by visual scoring of paw swelling and histology of ankle joints. Moreover, human RA synovial explants were incubated with 1 nM, 10 nM, or 100 nM of RvE1, and cytokine levels (IL-1ß, IL-6, IL-8, IL-10, INF-γ, and TNF-α) were measured using Luminex bead array. CIA triggered significant inflammation in the synovial cavity, proteoglycan loss, and cartilage and bone destruction in the ankle joints of mice. Prophylactic and therapeutic RvE1 regimens did not ameliorate CIA incidence and severity. Anti-TNF treatment significantly abrogated signs of joint inflammation, bone erosion, and proteoglycan depletion, but additional RvE1 treatment did not further reduce the anti-TNF-mediated suppression of the disease. Treatment with different concentrations of RvE1 did not decrease the expression of proinflammatory cytokines in human RA synovial explants in the studied conditions. Collectively, our findings demonstrated that RvE1 treatment was not an effective approach to treat CIA in DBA1/J mice in both prophylactic and therapeutic strategies. Furthermore, no effects were noticed when human synovial explants were incubated with different concentrations of RvE1.
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Artrite Experimental/sangue , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Citocinas/sangue , Ácido Eicosapentaenoico/análogos & derivados , Animais , Ácido Eicosapentaenoico/uso terapêutico , Interleucina-10/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos DBA , Estudos Prospectivos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangueRESUMO
The association between rheumatoid arthritis (RA) and periodontal disease (PD) has been the focus of numerous investigations driven by their common pathological features. RA is an autoimmune disease characterized by chronic inflammation, the production of anti-citrullinated proteins antibodies (ACPA) leading to synovial joint inflammation and destruction. PD is a chronic inflammatory condition associated with a dysbiotic microbial biofilm affecting the supporting tissues around the teeth leading to the destruction of mineralized and non-mineralized connective tissues. Chronic inflammation associated with both RA and PD is similar in the predominant adaptive immune phenotype, in the imbalance between pro- and anti-inflammatory cytokines and in the role of smoking and genetic background as risk factors. Structural damage that occurs in consequence of chronic inflammation is the ultimate cause of loss of function and disability observed with the progression of RA and PD. Interestingly, the periodontal pathogen Porphyromonas gingivalis has been implicated in the generation of ACPA in RA patients, suggesting a direct biological intersection between PD and RA. However, more studies are warranted to confirm this link, elucidate potential mechanisms involved, and ascertain temporal associations between RA and PD. This review is mainly focused on recent clinical and translational research intends to discuss and provide an overview of the relationship between RA and PD, exploring the similarities in the immune-pathological aspects and the possible mechanisms linking the development and progression of both diseases. In addition, the current available treatments targeting both RA and PD were revised.
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Anticorpos Antiproteína Citrulinada/metabolismo , Artrite Reumatoide/imunologia , Periodontite/microbiologia , Citocinas/metabolismo , Progressão da Doença , Disbiose/imunologia , Disbiose/microbiologia , Regulação da Expressão Gênica , Humanos , Periodontite/imunologia , Porphyromonas gingivalis/imunologiaRESUMO
PURPOSE: To investigate the effectiveness of adding leukocyte and platelet-rich fibrin (L-PRF) to deproteinized bovine bone mineral (DBBM) for early implant placement after maxillary sinus augmentation. MATERIALS AND METHODS: Twelve patients requiring two-stage bilateral maxillary sinus augmentation were enrolled to the study. The elevated sinus cavities were randomly grafted with DBBM + L-PRF (test) or DBBM alone (control) in a split-mouth design. Implants were placed in the augmented sites after 4 months in the test group and 8 months in the control group. Bone biopsies were collected during implant placement for histomorphometric evaluation. Resonance frequency analysis was performed immediately after implant placement and at implant loading in both groups. Cone-beam computed tomography was obtained preoperatively and postoperatively for evaluation of graft volume changes. RESULTS: Both procedures were effective for maxillary sinus augmentation. Cone-beam computed tomography analysis did not reveal differences in graft volume between test and control group at any of the evaluated time points (P > .05). Histological evaluation demonstrated increased percentage of newly formed bone for the test group (44.58% ± 13.9%) compared to the control group (30.02% ± 8.42%; P = .0087). The amount of residual graft in the control group was significantly higher (13.75% ± 9.99%) than in the test group (3.59 ± 4.22; P = .0111). Implant stability quotient (ISQ) immediately after implant placement was significantly higher in the control group (75.13 ± 5.69) compared to the test group (60.9 ± 9.35; P = .0003). The ISQ values at loading did not differ between the groups (P = .8587). Implant survival rate was 100% for both groups. CONCLUSION: The addition of L-PRF to the DBBM into the maxillary sinus allowed early implant placement (4 months) with increased new bone formation than DBBM alone after 8 months of healing.
Assuntos
Substitutos Ósseos , Seio Maxilar , Fibrina Rica em Plaquetas , Levantamento do Assoalho do Seio Maxilar , Animais , Transplante Ósseo , Bovinos , Implantação Dentária Endóssea , Humanos , Leucócitos , MineraisRESUMO
OBJECTIVES: The aim of this study was to investigate bone turnover alterations after alendronate (ALD) withdrawal and its influence on dental implants osseointegration. MATERIALS AND METHODS: Seventy female Wistar rats were randomly divided in 2 groups that received on day 0 either placebo (control group-CTL; n = 10) or 1 mg/kg sodium alendronate (ALD; n = 60) once a week for 4 months. At day 120, ALD treatment was suspended for 50 animals. Then, a titanium implant was placed in the left tibia of each rat that were randomly allocated in five subgroups of ten animals each, according to the period of evaluation: day 0 (INT-0), day 7 (INT-7), day 14 (INT-14), day 28 (INT-28), and day 45 (INT-45) after ALD withdrawal. CTL group and a group that received ALD until the end of the experimental period (non-interrupted group-non-INT; n = 10) underwent implant placement on day 120. Animals were euthanized 28 days after implant surgery. Bone mineral density (BMD) of femur and lumbar vertebrae were evaluated by DXA, biochemical markers of bone turnover were analyzed by ELISA, and bone histomorphometry was performed to measure bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO). RESULTS: All groups receiving ALD showed higher BMD values when compared to CTL group, which were maintained after its withdrawal. Decreased concentrations in all bone turnover markers were observed in the non-INT group, and in the groups in which ALD was discontinued compared to the CTL group. The non-INT group showed lower %BIC and notably changes in bone quality, which was persistent after drug withdrawal. CONCLUSION: Collectively, the findings of this study demonstrated that ALD therapy decreased bone turnover and impaired bone quality and quantity around dental implants, and that its discontinuation did not reverse these findings. CLINICAL RELEVANCE: The severe suppression of bone turnover caused by the prolonged use of ALD may alter the capacity of bone tissue to integrate with the implant threads impairing the osseointegration process.