RESUMEN
Purpose: Oxidative stress and mitochondrial dysfunction are potential contributors to the compromised tissue regeneration capacity of alveolar bone in diabetic patients. Berberine, an active plant alkaloid, exhibits multiple pharmacological effects including antioxidation, blood glucose- and blood lipid-lowering properties. However, it remains uncertain whether berberine can improve impaired osteogenesis in type 2 diabetes mellitus (T2DM), and its poor solubility and oral bioavailability also constrain its applications in bone regeneration. Thus, our study aimed to probe the effects of berberine on bone marrow stem cells (BMSCs) in a diabetic microenvironment, with a greater emphasis on developing a suitable nano-delivery system for berberine and assessing its capability to repair diabetic alveolar bone defects. Methods: Firstly, BMSCs were exposed to berberine within a high glucose and palmitate (HG+PA) environment. Reactive oxygen species levels, mitochondrial membrane potential, ATP generation, cell apoptosis, and osteogenic potential were subsequently assessed. Next, we explored the regulatory mechanism of autophagy flux in the positive effects of berberine. Furthermore, a nanocarrier based on emulsion electrospinning for sustained local delivery of berberine (Ber@SF/PCL) was established. We assessed its capacity to enhance bone healing in the alveolar bone defect of T2DM rats through micro-computed tomography and histology analysis. Results: Berberine treatment could inhibit reactive oxygen species overproduction, mitochondrial dysfunction, apoptosis, and improve osteogenesis differentiation by restoring autophagy flux under HG+PA conditions. Notably, Ber@SF/PCL electrospun nanofibrous membrane with excellent physicochemical properties and good biological safety had the potential to promote alveolar bone remodeling in T2DM rats. Conclusion: Our study shed new lights into the protective role of berberine on BMSCs under T2DM microenvironment. Furthermore, berberine-loaded composite electrospun membrane may serve as a promising approach for regenerating alveolar bone in diabetic patients.
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Berberina , Regeneración Ósea , Diabetes Mellitus Experimental , Células Madre Mesenquimatosas , Mitocondrias , Especies Reactivas de Oxígeno , Berberina/farmacología , Berberina/administración & dosificación , Berberina/química , Berberina/farmacocinética , Animales , Especies Reactivas de Oxígeno/metabolismo , Regeneración Ósea/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Ratas , Células Madre Mesenquimatosas/efectos de los fármacos , Masculino , Diabetes Mellitus Experimental/tratamiento farmacológico , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Ratas Sprague-Dawley , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Portadores de Fármacos/química , Pérdida de Hueso Alveolar/tratamiento farmacológico , Palmitatos/química , Palmitatos/farmacología , Células CultivadasRESUMEN
This study aimed to investigate the impact of minocycline on the alveolar bone in experimental periodontitis in rats. Thirty Wistar rats were randomly assigned to three groups: control without periodontitis; experimental periodontitis induced by ligature; experimental periodontitis + intraperitoneal administration minocycline for seven days. Ligatures remained in place in both periodontitis groups for 14 days. At the end of the experiment, the animals were euthanized and one hemimandible underwent micro-computed tomography (micro-CT) analysis to assess vertical bone loss and alveolar bone quality. Histopathological analysis was performed on the other hemimandible. Statistical analysis was performed using ANOVA with Tukey's post-test (p<0.05). The results showed a significant reduction in vertical bone loss in the animals treated with minocycline compared with untreated animals. Minocycline also preserved the alveolar bone thickness, number, spacing, and bone volume to tissue volume ratio. Histopathological analysis indicated that minocycline reduced bone resorption, decreased inflammatory response, and maintained the bone collagen fibers. This study demonstrated the effectiveness of minocycline in reducing vertical bone loss and preserved bone quality in rats with experimental periodontitis. The results of this study indicate that minocycline has the potential to serve as an additional treatment option for periodontitis. However, further research is warranted to assess the efficacy and safety of minocycline use in patients with periodontitis.
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Pérdida de Hueso Alveolar , Minociclina , Periodontitis , Ratas Wistar , Microtomografía por Rayos X , Animales , Minociclina/farmacología , Minociclina/uso terapéutico , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/patología , Pérdida de Hueso Alveolar/diagnóstico por imagen , Pérdida de Hueso Alveolar/prevención & control , Periodontitis/tratamiento farmacológico , Periodontitis/patología , Ratas , Masculino , Modelos Animales de Enfermedad , Antibacterianos/farmacología , Antibacterianos/uso terapéuticoRESUMEN
Object: The present study intended to evaluate the effect of simvastatin-loaded nanomicelles (SVNs) on promoting new bone formation and reducing alveolar ridge resorption at the tooth extraction sites at the early healing of the extraction sockets. Methods: SVNs were synthesized using a dialysis method. The rabbit tooth extraction model was established, SVNs and simvastatin (SV) were loaded on gelatin sponge and inserted into the extraction socket. CBCT scans were performed at 0, 2, and 4 weeks postoperatively to evaluate bone formation and alveolar ridge absorption in the extraction sockets. And all the animals were sacrificed and the mandibles were harvested. And HE staining and Masson staining were used for histological evaluation of the bone formation in the extraction sockets. Results: Radiographic evaluation showed that compared with the blank control group, at 2 and 4 weeks after extraction, SVNs increased the new bone density in the extraction sockets by 75.7% and 96.5%, and reduced the absorption rate of alveolar ridge length at the extraction sites by 60.8% and 49.1%, respectively. Histological evaluation showed that SVNs significantly improved the maturation of new bone tissue in the extraction sockets. Conclusion: SVNs can significantly accelerate healing and effectively reduce the absorption of alveolar ridge at the extraction sites in the early stage of tooth extraction socket healing.
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Micelas , Simvastatina , Extracción Dental , Alveolo Dental , Animales , Conejos , Simvastatina/farmacología , Simvastatina/administración & dosificación , Simvastatina/farmacocinética , Simvastatina/química , Alveolo Dental/efectos de los fármacos , Alveolo Dental/diagnóstico por imagen , Cicatrización de Heridas/efectos de los fármacos , Pérdida de Hueso Alveolar/prevención & control , Pérdida de Hueso Alveolar/diagnóstico por imagen , Pérdida de Hueso Alveolar/tratamiento farmacológico , Proceso Alveolar/efectos de los fármacos , Proceso Alveolar/diagnóstico por imagen , Osteogénesis/efectos de los fármacos , Masculino , Nanopartículas/químicaRESUMEN
Dental implants are a reliable treatment option for restoring missing teeth, but adequate bone quantity and quality are crucial for success. This case series presents four cases treated by different clinicians, all following very similar concepts for combined periodontal and vertical ridge augmentation using recombinant human platelet-derived growth factor-BB. All cases involved a severe periodontal defect requiring either extraction of the adjacent tooth or periodontal regeneration. Different bone grafts and membrane types were utilised. Although true periodontal regeneration cannot be said categorically to have occurred due to a lack of histological evidence, the clinical and radiographic findings suggest almost complete bone fill in all cases. This case series demonstrates that combined periodontal and vertical ridge augmentation using recombinant human platelet-derived growth factor-BB could be successful, but proper case selection and patient preparation for the possibility of multiple surgical procedures are recommended. Conflict-of-interest statement: At the time of preparing this manuscript, Dr Saleh was a clinical advisor for Lynch Biologics, Franklin, TN, USA. The other authors declare that they have no conflicts of interest relating to this study.
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Aumento de la Cresta Alveolar , Becaplermina , Humanos , Femenino , Masculino , Aumento de la Cresta Alveolar/métodos , Persona de Mediana Edad , Becaplermina/uso terapéutico , Adulto , Proteínas Recombinantes/uso terapéutico , Regeneración Ósea/efectos de los fármacos , Pérdida de Hueso Alveolar/cirugía , Pérdida de Hueso Alveolar/tratamiento farmacológico , Trasplante Óseo/métodos , Proteínas Proto-Oncogénicas c-sis/uso terapéutico , Regeneración Tisular Guiada Periodontal/métodosRESUMEN
G protein-coupled receptor (GPR)40 and GPR120 are receptors for medium- and long-chain free fatty acids. It has been well documented that GPR40 and GPR120 activation improves metabolic syndrome (MetS) and exerts anti-inflammatory effects. Since chronic periodontitis is a common oral inflammatory disease initiated by periodontal pathogens and exacerbated by MetS, we determined if GPR40 and GPR120 activation with agonists improves MetS-associated periodontitis in animal models in this study. We induced MetS and periodontitis by high-fat diet feeding and periodontal injection of lipopolysaccharide, respectively, and treated mice with GW9508, a synthetic GPR40 and GPR120 dual agonist. We determined alveolar bone loss, osteoclast formation, and periodontal inflammation using micro-computed tomography, osteoclast staining, and histology. To understand the underlying mechanisms, we further performed studies to determine the effects of GW9508 on osteoclastogenesis and proinflammatory gene expression in vitro. Results showed that GW9508 improved metabolic parameters, including glucose, lipids, and insulin resistance. Results also showed that GW9508 improves periodontitis by reducing alveolar bone loss, osteoclastogenesis, and periodontal inflammation. Finally, in vitro studies showed that GW9508 inhibited osteoclast formation and proinflammatory gene secretion from macrophages. In conclusion, this study demonstrated for the first time that GPR40/GPR120 agonist GW9508 reduced alveolar bone loss and alleviated periodontal inflammation in mice with MetS-exacerbated periodontitis, suggesting that activating GPR40/GPR120 with agonist GW9508 is a potential anti-inflammatory approach for the treatment of MetS-associated periodontitis.
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Síndrome Metabólico , Metilaminas , Periodontitis , Propionatos , Receptores Acoplados a Proteínas G , Animales , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/metabolismo , Ratones , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/metabolismo , Síndrome Metabólico/complicaciones , Propionatos/farmacología , Propionatos/uso terapéutico , Periodontitis/tratamiento farmacológico , Periodontitis/metabolismo , Metilaminas/farmacología , Masculino , Ratones Endogámicos C57BL , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/etiología , Dieta Alta en Grasa/efectos adversos , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Modelos Animales de Enfermedad , Osteogénesis/efectos de los fármacosRESUMEN
INTRODUCTION: Periodontitis (PD) is a chronic inflammatory disease leading to alveolar bone loss. This study investigated the effect of nootkatone and regulatory mechanism in reducing periodontal inflammation and alveolar bone loss in a rat model. MATERIAL AND METHODS: Twenty male Sprague-Dawley rats were divided into control, periodontitis, and nootkatone-treated groups (45 or 90 mg/kg). Ligature induction method was adopted to establish the PD model. After 21 days, rats received daily gavage of either saline or nootkatone for 10 days. Alveolar bone loss was assessed using micro-CT. Histological analyses included hematoxylin and eosin (H&E), tartrate-resistant acid phosphatase (TRAP), and Masson's trichrome stainings. Immunohistochemistry for heme oxygenase 1 (HO-1) and nuclear factor erythroid-2 related factor 2 (Nrf2) were performed in periodontal tissues. Content of inflammatory cytokines IL-1ß, IL-6, and TNF-α in gingival tissues around ligature were assessed using ELISA kits. Malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were analyzed and Western blot for NF-κB expression in gingival tissues were performed. RESULTS: Nootkatone significantly reduced the distance from cementoenamel junction to alveolar bone crest (CEJ-ABC), enhanced bone mineral density (BMD), bone volume (BV), and BV/total volume (TV) ratio in ligature-induced rats. Higher dose of nootkatone (90 mg/kg) did not show more significant therapeutic effect than lower dose (45 mg/kg). Histological staining showed decreased osteoclasts' number and improved bone architecture in the nootkatone group. Content of IL-1ß, IL-6, and TNF-α and inflammatory cell infiltration level in gingival tissues around the ligature were decreased in the nootkatone-treatment rats. Nootkatone increased Nrf2 and HO-1 protein expression and decreased NF-κB protein level, suppressing MDA levels and enhancing SOD activity. CONCLUSIONS: In a rat model, nootkatone effectively mitigates periodontal inflammation and alveolar bone loss through the Nrf2/HO-1 and NF-κB pathways. These findings suggest nootkatone as a promising therapeutic agent for the treatment of periodontitis.
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Pérdida de Hueso Alveolar , Modelos Animales de Enfermedad , Factor 2 Relacionado con NF-E2 , FN-kappa B , Periodontitis , Ratas Sprague-Dawley , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Masculino , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/metabolismo , Pérdida de Hueso Alveolar/prevención & control , Periodontitis/tratamiento farmacológico , Periodontitis/metabolismo , FN-kappa B/metabolismo , Ratas , Sesquiterpenos Policíclicos/farmacología , Sesquiterpenos Policíclicos/uso terapéutico , Transducción de Señal/efectos de los fármacos , Hemo-Oxigenasa 1/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Hemo Oxigenasa (Desciclizante)RESUMEN
Treatments to reduce periodontal inflammation and rescue periodontitis bone resorption have been of interest to researchers. Bone tissue engineering materials have been gradually used in the treatment of bone defects, but periodontal bone tissue regeneration still faces challenges. Considering the biocompatibility factor, constructing bionic scaffolds with natural extracellular matrix properties is an ideal therapeutic pathway. Based on the pathological mechanism of periodontitis, in this study, short peptide and nanometer inorganic particles were comingled to construct NapKFF-nano CaF2 supramolecular composite hydrogels with different ratios. Material characterization experiments confirmed that the composite hydrogel had suitable mechanical properties and a three-dimensional structure that can function in the resorption region of the alveolar bone and provide spaces for cell proliferation and adhesion. The release of low concentrations of fluoride and calcium ions has been shown to have positive biological effects in both in vivo and in vitro experiments. Vitro experiments confirmed that the composite hydrogel had good biocompatibility and promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Microbiological experiments confirmed that the composite hydrogel inhibited the activity of periodontal pathogenic bacteria. In animal studies, composite hydrogel applied to periodontitis rats in vivo can effectively repair alveolar bone resorption. This composite hydrogel has a simple preparation method and is inexpensive to produce, yet it has antibacterial and osteogenesis-promoting incremental effects, which makes it well suited for the treatment of periodontitis bone resorption, providing a new strategy for periodontal bone tissue engineering.
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Hidrogeles , Células Madre Mesenquimatosas , Nanopartículas , Osteogénesis , Periodontitis , Animales , Hidrogeles/química , Hidrogeles/farmacología , Periodontitis/tratamiento farmacológico , Periodontitis/patología , Ratas , Nanopartículas/química , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Osteogénesis/efectos de los fármacos , Fluoruro de Calcio/química , Fluoruro de Calcio/farmacología , Ratas Sprague-Dawley , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/patología , Masculino , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/patología , Regeneración Ósea/efectos de los fármacos , Diferenciación Celular/efectos de los fármacosRESUMEN
Metformin has shown outstanding anti-inflammatory and osteogenic abilities. Mesenchymal stem cell-derived extracellular vesicles (EVs) reveal promising therapeutic potency by carrying various biomolecules. This study explored the effects of metformin on the therapeutic potential of EVs derived from human periodontal ligament stem cells (PDLSCs) for periodontitis. PDLSCs were cultured in osteogenic medium with or without metformin, and the supernatant was then collected separately to extract EVs and metformin-treated EVs (M-EVs). After identifying the characteristics, we evaluated the anti-inflammatory and osteogenic effects of EVs and M-EVs in vivo and in vitro. Osteogenic differentiation of PDLSCs was markedly enhanced after metformin treatment, and the effect was dramatically inhibited by GW4896, an inhibitor of EVs' secretion. Metformin significantly increased EVs' yields and improved their effects on cell proliferation, migration, and osteogenic differentiation. Moreover, metformin significantly enhanced the osteogenic ability of EVs on inflammatory PDLSCs. Animal experiments revealed that alveolar bone resorption was dramatically reduced in the EVs and M-EVs groups when compared to the periodontitis group, while the M-EVs group showed the lowest levels of alveolar bone loss. Metformin promoted the osteogenic differentiation of PDLSCs partly through EVs pathway and significantly enhanced the secretion of PDLSCs-EVs with superior pro-osteogenic and anti-inflammatory potential, thus improving EVs' therapeutic potential on periodontitis.
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Diferenciación Celular , Vesículas Extracelulares , Metformina , Osteogénesis , Ligamento Periodontal , Periodontitis , Células Madre , Metformina/farmacología , Ligamento Periodontal/citología , Ligamento Periodontal/efectos de los fármacos , Ligamento Periodontal/metabolismo , Humanos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/efectos de los fármacos , Periodontitis/tratamiento farmacológico , Periodontitis/metabolismo , Osteogénesis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Células Madre/efectos de los fármacos , Células Madre/metabolismo , Animales , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Masculino , Movimiento Celular/efectos de los fármacos , Ratones , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/metabolismoRESUMEN
Periodontitis is a chronic inflammatory disease that affects about 45 %-50 % of adults worldwide, but the efficacy of current clinical therapies is unsatisfactory due to the complicated periodontal immune microenvironment. Thus, developing drugs that can regulate innate immune cells (e.g., macrophages) is a potent strategy to treat periodontitis. Here, we report that phloretin, a food plant-derived natural compound, is sufficient to alleviate periodontitis through immune regulation. In vivo, phloretin treatment could significantly reduce alveolar bone resorption and periodontal inflammation in mouse periodontitis models. In vitro, phloretin could suppress proinflammatory (M1-like) polarization and cytokine release in macrophages induced by LPS. Mechanistically, the immune regulatory role of phloretin in macrophages may be due to its metabolic regulation effect. Phloretin might restore the balance of M1/M2 macrophage transition in periodontitis by inhibiting HIF-1α-mediated glycolysis and PI3k/Akt pathways, thereby reducing the proinflammatory effect and immune disorder caused by over-activated M1 macrophages. Together, this study highlights that natural compound, such as phloretin, can restore periodontal immune homeostasis by metabolic regulation of macrophages, which may provide novel insight into the treatment of periodontitis.
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Glucólisis , Homeostasis , Subunidad alfa del Factor 1 Inducible por Hipoxia , Macrófagos , Ratones Endogámicos C57BL , Periodontitis , Floretina , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Animales , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Floretina/farmacología , Floretina/uso terapéutico , Glucólisis/efectos de los fármacos , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Periodontitis/tratamiento farmacológico , Periodontitis/inmunología , Periodontitis/metabolismo , Homeostasis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Masculino , Lipopolisacáridos/inmunología , Humanos , Células RAW 264.7 , Modelos Animales de Enfermedad , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Citocinas/metabolismo , Pérdida de Hueso Alveolar/tratamiento farmacológicoRESUMEN
PURPOSE: To evaluate the effect of MB-PDT assisted essential therapy on angle resorption of lower anterior alveolar bone in patients with periodontitis. METHODS: Forty patients who were diagnosed with periodontitis stage III-IV or C, lower anterior teeth alveolar bone angle resorption, and periodontal pocket depth greater than 4 mm were selected from April 2018 to October 2020 in the Department of Periodontology and Oral Mucosal Diseases, Changsha Stomatological Hospital. The patients were randomly divided into control group and experimental group with 20 cases in each group. Compared with the control group which was only managed with essential treatment, the experimental group was treated with MB-PDT on the basis of the control group. The plaque index (PLI) and gingival bleeding index (GBI) scores of the two groups were recorded before surgery and 1 and 2 weeks after surgery. Probing depth (PD) and clinical attachment level (CAL) were detected before and 6 months after surgery. Statistical analysis of the data was performed using Graphpad Prism 5 software package. RESULTS: The PLI and GBI of the experimental group were significantly lower than those of the control group at 1 and 2 weeks after operation(Pï¼0.05). Six months after surgery, PD and CAL levels in the experimental group were significantly lower than those in the control group (Pï¼0.05). CONCLUSIONS: MB-PDT adjuvant therapy has the advantages of simple operation, efficient sterilization, promotion of healing, and high safety performance. It may be a new non-surgical adjuvant treatment strategy for effective treatment of lower anterior alveolar angular resorption.
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Pérdida de Hueso Alveolar , Índice de Placa Dental , Índice Periodontal , Humanos , Pérdida de Hueso Alveolar/terapia , Pérdida de Hueso Alveolar/tratamiento farmacológico , Fotoquimioterapia/métodos , Periodontitis/tratamiento farmacológico , Periodontitis/terapia , Mandíbula/efectos de los fármacosRESUMEN
OBJECTIVES: Botulinum toxin is used in human in repeatedly masticatory muscles injections. A single BTX injection in animal induces mandibular bone loss with a muscle enthesis hypertrophic metaplasia. Our aim was to evaluate mandibular bone changes after unilateral repeated injections of BTX in adult rats. STUDY DESIGN: Mature male rats were randomized into 3 groups: one, two or three injections. Each rat received injections in right masseter and temporalis muscles. The left side was the control side. Microcomputed tomography was used to perform 2D and 3D analyses. RESULTS: Bone loss was evidenced on the right sides of alveolar and condylar bone. Alveolar bone volume increased in both control left side and injected right side whereas condylar bone volume remained constant in all groups, for both sides. Enthesis bone hypertrophic metaplasias were evidenced on the BTX injected sides without any modification with the number of injections. CONCLUSION: BTX repeated injections in masticatory muscles lead to major mandibular condylar and alveolar bone loss that does not worsen. They lead to the occurrence of an enthesis bone proliferation that is not dependent on the number of injections. These results are an argument for the safety of BTX injections in masticatory muscles in human.
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Pérdida de Hueso Alveolar , Cóndilo Mandibular , Microtomografía por Rayos X , Animales , Ratas , Masculino , Pérdida de Hueso Alveolar/patología , Pérdida de Hueso Alveolar/tratamiento farmacológico , Cóndilo Mandibular/efectos de los fármacos , Cóndilo Mandibular/patología , Inyecciones Intramusculares , Distribución Aleatoria , Músculos Masticadores/efectos de los fármacos , Músculos Masticadores/patología , Ratas Wistar , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas/administración & dosificación , Músculo Masetero/efectos de los fármacos , Músculo Masetero/patología , Hipertrofia/tratamiento farmacológico , Hipertrofia/patologíaRESUMEN
Background and Objectives: Unfavorable intrabony defects (IBDs) are associated with the progression of periodontal disease and tooth loss. Growing scientific evidence has demonstrated the effectiveness of platelet concentrations in periodontal treatment. The aim of our study was to demonstrate the non-inferiority of an autogenous bone graft (ABG) associated with leukocyte- and platelet-rich fibrin (L-PRF) compared to ABG + Collagen Membrane in the treatment of IBDs. Material and Methods: Sixty-four patients with at least one IBD were randomly assigned to two groups: ABG+L-PRF and CM+ABG. Clinical and radiographic evaluations were performed at baseline and 12-month follow-up. Clinical attachment level (CAL), gingival recession (GR), probing pocket depth (PPD), and radiograph defect bone level (DBL) were compared between the two treatments. To evaluate the effectiveness of ABG+L-PRF, a non-inferiority margin of =1 mm (-1 mm for GR) was chosen; a second non-inferiority margin of =0.5 mm (-0.5 mm for GR) was set for clinical relevance. Results: At 12-month follow up, both treatments showed clinical and radiographic improvements. The 90% confidence intervals of the CM+ABG-L-PRF+ABG mean difference for CAL gain (-0.0564 mm [-0.316 to 0.203]), DBL gain (-0.433 mm [-0.721 to -0.145]), and PPD reduction (0.232 mm [0.015 to 0.449]) were below the 0.5 mm non-inferiority margin; the GR increase (0.255 mm [0.0645 to 0.445]) stayed above the -0.5 mm. Conclusions: the L-PRF+ABG treatment of unfavorable IBDs is non-inferior with respect to the CM+ABG therapy for CAL gain, but with a lower GR, a slightly higher PPD, and DBL gain.
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Trasplante Óseo , Colágeno , Fibrina Rica en Plaquetas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Colágeno/uso terapéutico , Adulto , Trasplante Óseo/métodos , Leucocitos , Pérdida de Hueso Alveolar/cirugía , Pérdida de Hueso Alveolar/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Periodontitis is a widely prevalent oral disease around the world characterized by the disruption of the periodontal ligament and the subsequent development of periodontal pockets, as well as the loss of alveolar bone, and may eventually lead to tooth loss. This research aims to assess the suppressive impact of Eupatilin, a flavone obtained from Artemisia argyi, on osteoclastogenesis in vitro and periodontitis in vivo. We found that Eupatilin can efficiently obstruct the differentiation of Raw264.7 and bone marrow-derived macrophages (BMDMs) induced by RANKL, leading to the formation of mature osteoclasts. Consistently, bone slice resorption assay showed that Eupatilin significantly inhibited osteoclast-mediated bone resorption in a dose-dependent manner. Eupatilin also downregulated the expression of osteoclast-specific genes and proteins in Raw264.7 and BMDMs. RNA sequencing showed that Eupatilin notably downregulated the expression of Siglec-15. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses identified significantly enriched pathways in DEGs, including MAPK signaling pathway. And further mechanistic investigations confirmed that Eupatilin repressed MAPKs/NF-κBsignaling pathways. It was found that Siglec-15 overexpression reversed the inhibitory impact of Eupatilin on the differentiation of osteoclasts. Furthermore, activating MAPK signaling pathway reversed the downregulation of Siglec-15 and the inhibition of osteoclastogenesis by Eupatilin. To sum up, Eupatilin reduced the expression of Siglec-15 by suppressing MAPK signaling pathway, ultimately leading to the inhibition of osteoclastogenesis. Meanwhile, Eupatilin suppressed the alveolar bone resorption caused by experimentalperiodontitis in vivo. Eupatilin exhibits potential therapeutic effects in the treatment of periodontitis, rendering it a promising pharmaceutical agent.
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Pérdida de Hueso Alveolar , Flavonoides , Osteoclastos , Osteogénesis , Periodontitis , Animales , Ratones , Osteogénesis/efectos de los fármacos , Células RAW 264.7 , Flavonoides/farmacología , Flavonoides/uso terapéutico , Pérdida de Hueso Alveolar/tratamiento farmacológico , Osteoclastos/efectos de los fármacos , Periodontitis/tratamiento farmacológico , Ratones Endogámicos C57BL , Diferenciación Celular/efectos de los fármacos , Masculino , Macrófagos/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Artemisia/química , Ligando RANK/metabolismoRESUMEN
To develop novel bovine lactoferrin (bLF) peptides targeting bLF-tumour necrosis factor (TNF) receptor-associated factor 6 (TRAF6) binding sites, we identified two peptides that could target bLF-TRAF6 binding sites using structural analysis. Moreover, another peptide that could bind to the TRAF6 dimerization area was selected from the bLF sequence. The effects of each peptide on cytokine expression in lipopolysaccharide (LPS)-stimulated osteoblasts (ST2) and on osteoclastogenesis were examined using an LPS-treated co-culture of primary bone marrow cells (BMCs) with ST2 cells and a single culture of osteoclast precursor cells (RAW-D) treated with soluble receptor activator of NF-κB ligand. Finally, the effectiveness of these peptides against LPS-induced alveolar bone destruction was assessed. Two of the three peptides significantly suppressed LPS-induced TNF-α and interleukin-1ß expression in ST2 cells. Additionally, these peptides inhibited and reversed LPS-induced receptor activator of NF-κB ligand (RANKL) upregulation and osteoprotegerin (OPG) downregulation, respectively. Furthermore, both peptides significantly reduced LPS-induced osteoclastogenesis in the BMC-ST2 co-culture and RANKL-induced osteoclastogenesis in RAW-D cells. In vivo, topical application of these peptides significantly reduced the osteoclast number by downregulating RANKL and upregulating OPG in the periodontal ligament. It is indicated that the novel bLF peptides can be used to treat periodontitis-associated bone destruction.
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Lactoferrina , Lipopolisacáridos , Osteoclastos , Péptidos , Animales , Lactoferrina/farmacología , Lactoferrina/química , Lactoferrina/metabolismo , Lipopolisacáridos/farmacología , Ratas , Péptidos/farmacología , Péptidos/química , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Ligando RANK/metabolismo , Masculino , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/metabolismo , Pérdida de Hueso Alveolar/patología , Bovinos , Ratones , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteoblastos/citología , Ratas Sprague-Dawley , Osteogénesis/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Sitios de Unión , Técnicas de Cocultivo , Osteoprotegerina/metabolismo , Modelos Animales de EnfermedadRESUMEN
AIMS: This study aimed to investigate the effects of Umbelliferone (UMB) on the inflammation underlying alveolar bone resorption in mouse periodontitis. METHODS: Male Swiss mice subjected to a ligature of molars were grouped as non-treated (NT), received UMB (15, 45, or 135 mg/kg) or saline daily for 7 days, respectively, and were compared with naïve mice as control. Gingival tissues were evaluated by myeloperoxidase (MPO) activity and interleukin-1ß level by ELISA. The bone resorption was directly assessed on the region between the cement-enamel junction and the alveolar bone crest. Microscopically, histomorphometry of the furcation region, immunofluorescence for nuclear factor-kappa B (NF-ĸB), and immunohistochemistry for tartrate-resistant acid phosphatase (TRAP), and cathepsin K (CTSK) were performed. Systemically, body mass variation and leukogram were analyzed. RESULTS: Periodontitis significantly increased MPO activity, interleukin-1ß level, and NF-ĸB+ immunofluorescence, and induced severe alveolar bone and furcation resorptions, besides increased TRAP+ and CTSK+ cells compared with naïve. UMB significantly prevented the inflammation by reducing MPO activity, interleukin-1ß level, and NF-ĸB+ intensity, besides reduction of resorption of alveolar bone and furcation area, and TRAP+ and CTSK+ cells compared with the NT group. Periodontitis or UMB treatment did not affect the animals systemically. CONCLUSION: UMB improved periodontitis by reducing inflammation and bone markers.
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Pérdida de Hueso Alveolar , Interleucina-1beta , Periodontitis , Umbeliferonas , Animales , Masculino , Ratones , Pérdida de Hueso Alveolar/prevención & control , Pérdida de Hueso Alveolar/patología , Pérdida de Hueso Alveolar/tratamiento farmacológico , Periodontitis/tratamiento farmacológico , Periodontitis/patología , Umbeliferonas/uso terapéutico , Umbeliferonas/farmacología , Osteoclastos/efectos de los fármacos , Osteoclastos/patología , FN-kappa B/metabolismo , Fosfatasa Ácida Tartratorresistente/metabolismo , Peroxidasa , Inflamación , Catepsina K , Ligadura , Encía/patología , Encía/efectos de los fármacosRESUMEN
AIM: To study the clinical, radiographic and microbiological outcomes after surgical treatment of peri-implantitis, with or without adjunctive systemic antibiotics. MATERIALS AND METHODS: Eighty-four patients (113 implants) with peri-implantitis were randomized into three groups (A, amoxicillin and metronidazole; B, phenoxymethylpenicillin and metronidazole; or C, placebo). Treatment included resective surgery and implant surface decontamination with adjunctive antibiotics or placebo. Primary outcomes were probing pocket depth (PPD) reduction and marginal bone level (MBL) stability. Secondary outcomes were treatment success (defined as PPD ≤ 5 mm, bleeding on probing [BOP] ≤ 1site, absence of suppuration on probing [SOP] and absence of progressive bone loss of >0.5 mm), changes in BOP/SOP, mucosal recession (REC), clinical attachment level (CAL), bacterial levels and adverse events. Outcomes were evaluated for up to 12 months. The impact of potential prognostic indicators on treatment success was evaluated using multilevel logistic regression analysis. RESULTS: A total of 76 patients (104 implants) completed the study. All groups showed clinical and radiological improvements over time. Statistically significant differences were observed between groups for MBL stability (A = 97%, B = 89%, C = 76%), treatment success (A = 68%, B = 66%, C = 28%) and bacterial levels of Aggregatibacter actinomycetemcomitans and Tannerella forsythia, favouring antibiotics compared to placebo. Multiple regression identified antibiotic use as potential prognostic indicator for treatment success. Gastrointestinal disorders were the most reported adverse events in the antibiotic groups. CONCLUSIONS: Adjunctive systemic antibiotics resulted in additional improvements in MBL stability. However, the potential clinical benefits of antibiotics need to be carefully balanced against the risk of adverse events and possible antibiotic resistance.
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Amoxicilina , Antibacterianos , Metronidazol , Periimplantitis , Humanos , Periimplantitis/tratamiento farmacológico , Periimplantitis/microbiología , Periimplantitis/cirugía , Femenino , Masculino , Metronidazol/uso terapéutico , Metronidazol/administración & dosificación , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Persona de Mediana Edad , Amoxicilina/uso terapéutico , Amoxicilina/administración & dosificación , Resultado del Tratamiento , Anciano , Pérdida de Hueso Alveolar/cirugía , Pérdida de Hueso Alveolar/tratamiento farmacológico , Bolsa Periodontal/cirugía , Bolsa Periodontal/tratamiento farmacológico , Bolsa Periodontal/microbiología , Placebos , Estudios de Seguimiento , Pérdida de la Inserción Periodontal/cirugía , Pérdida de la Inserción Periodontal/tratamiento farmacológico , Recesión Gingival/cirugía , Recesión Gingival/tratamiento farmacológico , Adulto , Método Doble Ciego , Carga Bacteriana/efectos de los fármacosRESUMEN
Periodontal disease ranks third among noncommunicable illnesses, behind cancer and cardiovascular disease, and is closely related to the occurrence and progression of various systemic diseases. However, elucidating the processes of periodontal disease and promoting periodontal bone regeneration remains a challenge. Here, quercetin is demonstrated to reduce the oxidative stress state of orofacial mesenchymal stem cells (OMSCs) in vitro and to affect the osteogenic growth of OMSCs through molecular mechanisms that mediate the m6A change in Per1. Nevertheless, the limited therapeutic efficacy of systemic medication and the limitations of local medication resulting from the small, moist, and highly dynamic periodontal environment make it challenging to treat periodontal tissues with medication. Herein, a biosafe injectable hydrogel drug-controlled delivery system is constructed as a bone-enhancing factory and loaded with quercetin to treat oxidative stress injury in periodontal tissues. This drug-carrying system made up of nanoscale bioglass microspheres and a light-cured injectable hydrogel, allows effective drug particle loading and cementation in the dynamic and moist periodontal environment. Furthermore, the system demonstrates the ability to stimulate OMSCs osteogenic differentiation in a Per1-dependent manner, which ultimately promotes periodontal bone repair, suggesting that this system has potential for clinical periodontal therapy.
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Cerámica , Hidrogeles , Células Madre Mesenquimatosas , Estrés Oxidativo , Quercetina , Estrés Oxidativo/efectos de los fármacos , Cerámica/farmacología , Animales , Quercetina/farmacología , Quercetina/administración & dosificación , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Regeneración Ósea/efectos de los fármacos , Humanos , Osteogénesis/efectos de los fármacos , Modelos Animales de Enfermedad , Ratones , Pérdida de Hueso Alveolar/tratamiento farmacológicoRESUMEN
Orthodontic space closure following tooth extraction is often hindered by alveolar bone deficiency. This study investigates the therapeutic use of nuclear factor-kappa B (NF-κB) decoy oligodeoxynucleotides loaded with polylactic-co-glycolic acid nanospheres (PLGA-NfDs) to mitigate alveolar bone loss during orthodontic tooth movement (OTM) following the bilateral extraction of maxillary first molars in a controlled experiment involving forty rats of OTM model with ethics approved. The decreased tendency of the OTM distance and inclination angle with increased bone volume and improved trabecular bone structure indicated minimized alveolar bone destruction. Reverse transcription-quantitative polymerase chain reaction and histomorphometric analysis demonstrated the suppression of inflammation and bone resorption by downregulating the expression of tartrate-resistant acid phosphatase, tumor necrosis factor-α, interleukin-1ß, cathepsin K, NF-κB p65, and receptor activator of NF-κB ligand while provoking periodontal regeneration by upregulating the expression of alkaline phosphatase, transforming growth factor-ß1, osteopontin, and fibroblast growth factor-2. Importantly, relative gene expression over the maxillary second molar compression side in proximity to the alveolus highlighted the pharmacological effect of intra-socket PLGA-NfD administration, as evidenced by elevated osteocalcin expression, indicative of enhanced osteocytogenesis. These findings emphasize that locally administered PLGA-NfD serves as an effective inflammatory suppressor and yields periodontal regenerative responses following tooth extraction.
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Nanosferas , Oligodesoxirribonucleótidos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Técnicas de Movimiento Dental , Alveolo Dental , Animales , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Ratas , Nanosferas/química , Técnicas de Movimiento Dental/métodos , Oligodesoxirribonucleótidos/farmacología , Oligodesoxirribonucleótidos/administración & dosificación , Alveolo Dental/efectos de los fármacos , Alveolo Dental/patología , Masculino , FN-kappa B/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Pérdida de Hueso Alveolar/terapia , Pérdida de Hueso Alveolar/patología , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/metabolismo , Extracción DentalRESUMEN
ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Wang Y, Chen CY, Stathopoulou PG, Graham LK, Korostoff J, Chen YW. Efficacy of Antibiotics Used as an Adjunct in the Treatment of Peri-implant Mucositis and Peri-implantitis: A Systematic Review and Meta-analysis. Int J Oral Maxillofac Implants. 2022 Mar-Apr;37(2):235-249. doi:10.11607/jomi.9220. PMID: 35476853. SOURCE OF FUNDING: None. TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of data.
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Antibacterianos , Periimplantitis , Humanos , Pérdida de Hueso Alveolar/tratamiento farmacológico , Antibacterianos/uso terapéutico , Implantes Dentales , Periimplantitis/tratamiento farmacológico , Periimplantitis/terapia , Revisiones Sistemáticas como Asunto , Metaanálisis como AsuntoRESUMEN
OBJECTIVE: Periodontitis is an inflammatory condition induced by subgingival bacterial dysbiosis, resulting in inflammatory-mediated destruction of tooth-supporting structures, potentially leading to the formation of infrabony defects. This case report describes the treatment of a patient who presented with a combination 1-2-wall defect on tooth 21. To maintain the residual periodontal attachment and minimize esthetic consequences, a regenerative approach was performed using recombinant human platelet-derived growth factor-BB (rh-PDGF-BB) and ß-tricalcium phosphate (ß-TCP). MATERIALS AND METHODS: At the time of postscaling/root planing reevaluation, a 34-year-old Asian male initially diagnosed with molar/incisor pattern stage III grade C periodontitis exhibited a 6-mm residual probing depth on the mesiopalatal aspect of tooth 21. Periodontal regenerative surgery was performed using rh-PDGF-BB with ß-TCP, without the use of a membrane. RESULTS: At the 1-year follow-up, a significant reduction in probing depth and radiographic evidence of bone fill were observed. Additionally, re-entry surgery for implant placement at site tooth 23 confirmed bone fill in the defect on tooth 21. CONCLUSION: These results demonstrate the efficacy of rh-PDGF-BB with ß-TCP in enhancing periodontal regeneration and support its use as a treatment option when treating poorly contained infrabony defects in the esthetic zone.