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1.
Life Sci ; 269: 119073, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33460666

RESUMEN

AIMS: Coagulation is a common event that play a double-edged role in physiological and pathological process. Anti-coagulation methods were applied in joint surgery or scaffolds implantation to encourage new vascular formation and avoid coagulation block. However, whether anti-coagulation drug perform regulatory roles in bone structure is unknown. This study aims to explore a direct thrombin inhibitor, argatroban, effects on bone marrow stromal cells (BMSCs) and decipher the underlying mechanisms. MATERIALS AND METHODS: Argatroban effects on BMSCs were investigated in vivo and in vitro. The drug was applied in periodontal disease model mice and bone loss was evaluated by µCT and histology. BMSCs were treated with different doses argatroban or vehicle. Cellular reactions were analyzed using wound healing assay, qRT-PCR, Alizarin Red S staining and western blotting. KEY FINDINGS: We demonstrated that local injection of argatroban can rescue bone loss in periodontal disease in vivo. To explore the underlying mechanism, we examined that cell proliferation and differentiation capability. Proliferation and migration of BMSCs were both inhibited by applying lower dose of argatroban. Interestingly, without affecting osteoclastogenesis, osteogenic differentiation was significantly induced by argatroban, which were shown by extracellular mineralization and upregulation of early osteoblastic differentiation markers, alkaline phosphatase, Osteocalcin, transcription factors RUNX2 and Osterix. In addition, molecular analysis revealed that argatroban promoted ß-catenin nuclear translocation and led to an increase of osteogenesis through activating canonical Wnt signaling. SIGNIFICANCE: Taken together, our results show the novel application of the anti-coagulation compound argatroban in the commitment of BMSCs-based alveolar bone regeneration and remodeling.


Asunto(s)
Pérdida de Hueso Alveolar/prevención & control , Arginina/análogos & derivados , Células Madre Mesenquimatosas/citología , Osteogénesis , Periodontitis/complicaciones , Ácidos Pipecólicos/farmacología , Sulfonamidas/farmacología , Trombina/antagonistas & inhibidores , Vía de Señalización Wnt/efectos de los fármacos , Pérdida de Hueso Alveolar/etiología , Pérdida de Hueso Alveolar/metabolismo , Pérdida de Hueso Alveolar/patología , Animales , Antitrombinas/farmacología , Arginina/farmacología , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Endogámicos C57BL
3.
Cell Prolif ; 54(2): e12973, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33382502

RESUMEN

OBJECTIVES: NLRP3 inflammasome is a critical part of the innate immune system and plays an important role in a variety of inflammatory diseases. However, the effects of NLRP3 inflammasome on periodontitis have not been fully studied. MATERIALS AND METHODS: We used ligature-induced periodontitis models of NLRP3 knockout mice (NLRP3KO ) and their wildtype (WT) littermates to compare their alveolar bone phenotypes. We further used Lysm-Cre/RosanTnG mouse to trace the changes of Lysm-Cre+ osteoclast precursors in ligature-induced periodontitis with or without MCC950 treatment. At last, we explored MCC950 as a potential drug for the treatment of periodontitis in vivo and in vitro. RESULTS: Here, we showed that the number of osteoclast precursors, osteoclast differentiation and alveolar bone loss were reduced in NLRP3KO mice compared with WT littermates, by using ligature-induced periodontitis model. Next, MCC950, a specific inhibitor of the NLRP3 inflammasome, was used to inhibit osteoclast precursors differentiation into osteoclast. Further, we used Lysm-Cre/RosanTnG mice to demonstrate that MCC950 decreases the number of Lysm-Cre+ osteoclast precursors in ligature-induced periodontitis. At last, treatment with MCC950 significantly suppressed alveolar bone loss with reduced IL-1ß activation and osteoclast differentiation in ligature-induced periodontitis. CONCLUSION: Our findings reveal that NLRP3 regulates alveolar bone loss in ligature-induced periodontitis by promoting osteoclastic differentiation.


Asunto(s)
Pérdida de Hueso Alveolar/patología , Diferenciación Celular , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Osteoclastos/citología , Periodontitis/patología , Pérdida de Hueso Alveolar/metabolismo , Pérdida de Hueso Alveolar/prevención & control , Animales , Diferenciación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Inflamasomas/efectos de los fármacos , Inflamasomas/metabolismo , Interleucina-1beta/metabolismo , Lipopolisacáridos/farmacología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Osteoclastos/metabolismo , Osteogénesis/efectos de los fármacos , Periodontitis/tratamiento farmacológico , Periodontitis/etiología , Células Madre/citología , Células Madre/metabolismo , Sulfonas/farmacología , Sulfonas/uso terapéutico
4.
PLoS One ; 15(8): e0232731, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32817640

RESUMEN

This study evaluated the effects of the chronic consumption of different concentrations of alcohol on the experimental periodontitis (EP). 160 rats were divided into 4 groups: (EP-NT) rats with EP and no alcohol exposure; (EP-A14) rats with EP exposed to 14% alcohol; (EP-A25) rats with EP exposed to 25% alcohol; (EP-A36) rats with EP exposed to 36% alcohol. The animals from the EP-A14, EP-A25 and EP-A36 groups were subjected to different concentrations of alcohol 30 days before EP induction. The histological characteristics, percentage of bone in the furcation (PBF) and bone metabolism in the furcation region were evaluated. The PBF and tartrate-resistant acid phosphatase (TRAP) data were subjected to statistical analysis. The EP-A14, EP-A25 and EP-A36 groups had lower PBFs compared with the EP-NT group. A more severe inflammatory process and a greater number of TRAP+ cells were also observed. In the EP-A14, EP-A25 and EP-A36 groups, the inflammatory process became more severe as the ingested alcoholic concentration increased. An increase in RANKL immunolabeling and a significantly higher number of TRAP+ cells were also observed. We conclude that chronic alcohol consumption increases the severity of experimental periodontitis in a dose-dependent manner by increasing the magnitude of local inflammatory responses and stimulating alveolar bone resorption.


Asunto(s)
Pérdida de Hueso Alveolar/patología , Etanol/efectos adversos , Periodontitis/patología , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/fisiopatología , Animales , Masculino , Ratas , Ratas Wistar , Fosfatasa Ácida Tartratorresistente/metabolismo
5.
Acta Odontol Latinoam ; 33(1): 50-55, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32621600

RESUMEN

The purpose of this study was to evaluate aortic wall thickness after periodontal disease and/or obesity induction in a Wistar rat model.Sixty male Wistar rats were randomly divided into four groups: control (CT), periodontal disease (PD), obesity (OB), and obesity plus periodontal disease (OB+PD). Groups OB and OB+PD received cafeteria diet for 17 weeks. After they had acquired obesity (week 12), periodontal disease was induced by placing a silk ligature on the maxillary right second molar of groups PD and OB+PD. During the experimental period, body weight and Lee index were assessed. Mean alveolar bone loss (ABL) was evaluated, and aortas were prepared for histometric analysis of the aortic wall by ImageJ software. Body weight and Lee index increased in rats exposed to cafeteria diet. Mean ABL was higher in Groups PD and OB+PD than in control and OB (p<0.05). ABL was 18% higher in Group OB+PD than in Group PD, with statistically significant difference (p<0.001). Aortas were thicker in Groups OB and OB+PD than in control and PD groups, respectively (2.31mm ± 0.28 and 2.33 ± 0.29 vs. 2.18 ± 0.26 and 2.14 ± 0.27). Group OB differed significantly from the control group (p=0.036), and OB+PD and OB differed significantly from PD (p=0.004 and p= 0.001, respectively). Obesity alters aortic wall thickness in Wistar rats. However, the presence of periodontal disease did not affect the aortic wall thickness under the conditions of the present study.


Asunto(s)
Pérdida de Hueso Alveolar/etiología , Aterosclerosis , Ligadura/efectos adversos , Obesidad/complicaciones , Periodontitis/complicaciones , Pérdida de Hueso Alveolar/patología , Animales , Modelos Animales de Enfermedad , Masculino , Periodontitis/patología , Ratas , Ratas Wistar
6.
Sci Rep ; 10(1): 7823, 2020 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-32385413

RESUMEN

This study investigates the role of NLRP3 inflammasome and its main effector Caspase-1 in inflammation and alveolar bone resorption associated with periodontitis. Heat-killed Aggregatibacter actinomycetemcomitans (Aa) was injected 3x/week (4 weeks) into gingival tissues of wild-type (WT), Nlrp3-KO and Caspase1-KO mice. Bone resorption was measured by µCT and osteoclast number was determined by tartrate-resistant acid phosphatase (TRAP) staining. Inflammation was assessed histologically (H/E staining and immunofluorescence of CD45 and Ly6G). In vitro studies determined the influence of Nlrp3 and Caspase-1 in Rankl-induced osteoclast differentiation and activity and on LPS-induced expression of inflammation-associated genes. Bone resorption was significantly reduced in Casp1-KO but not in Nlrp3-KO mice. Casp1-KO mice had increased in osteoclast numbers, whereas the inflammatory infiltrate or on gene expression were similar to those of WT and Nlrp3-KO mice. Strikingly, osteoclasts differentiated from Nlrp3-deficient macrophages had increased resorbing activity in vitro. LPS-induced expression of Il-10, Il-12 and Tnf-α was significantly reduced in Nlrp3- and Casp1-deficient macrophages. As an inceptive study, these results suggest that Nlrp3 inflammasome does not play a significant role in inflammation and bone resorption in vivo and that Caspase-1 has a pro-resorptive role in experimental periodontal disease.


Asunto(s)
Pérdida de Hueso Alveolar/genética , Caspasa 1/genética , Inflamación/genética , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Periodontitis/genética , Aggregatibacter actinomycetemcomitans , Pérdida de Hueso Alveolar/microbiología , Pérdida de Hueso Alveolar/patología , Animales , Diferenciación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Encía/crecimiento & desarrollo , Encía/microbiología , Humanos , Inflamación/microbiología , Inflamación/patología , Interleucina-10/genética , Interleucina-12/genética , Ratones , Ratones Noqueados , Osteoclastos/microbiología , Osteoclastos/patología , Periodontitis/microbiología , Periodontitis/patología , Ligando RANK/genética , Factor de Necrosis Tumoral alfa/genética
7.
J Pathol ; 251(3): 323-335, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32418202

RESUMEN

The lymphatic system plays a crucial role in the maintenance of tissue fluid homeostasis and the immunological response to inflammation. The effects of lymphatic drainage dysfunction on periodontitis have not been well studied. Here we show that lymphatic vessel endothelial receptor 1 (LYVE1)+ /podoplanin (PDPN)+ lymphatic vessels (LVs) are increased in the periodontal tissues, with accumulation close to the alveolar bone surface, in two murine periodontitis models: rheumatoid arthritis (RA)-associated periodontitis and ligature-induced periodontitis. Further, PDPN+ /alpha-smooth muscle actin (αSMA)- lymphatic capillaries are increased, whereas PDPN+ /αSMA+ collecting LVs are decreased significantly in the inflamed periodontal tissues. Both mouse models of periodontitis have delayed lymph flow in periodontal tissues, increased TRAP-positive osteoclasts, and significant alveolar bone loss. Importantly, the local administration of adeno-associated virus for vascular endothelial growth factor C, the major growth factor that promotes lymphangiogenesis, increases the area and number of PDPN+ /αSMA+ collecting LVs, promotes local lymphatic drainage, and reduces alveolar bone loss in both models of periodontitis. Lastly, LYVE1+ /αSMA- lymphatic capillaries are increased, whereas LYVE1+ /αSMA+ collecting LVs are decreased significantly in gingival tissues of patients with chronic periodontitis compared with those of clinically healthy controls. Thus, our findings reveal an important role of local lymphatic drainage in periodontal inflammation-mediated alveolar bone loss. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Asunto(s)
Pérdida de Hueso Alveolar/prevención & control , Proceso Alveolar/metabolismo , Periodontitis Crónica/terapia , Terapia Genética , Linfa/metabolismo , Vasos Linfáticos/metabolismo , Maxilar/metabolismo , Factor C de Crecimiento Endotelial Vascular/biosíntesis , Factor C de Crecimiento Endotelial Vascular/genética , Pérdida de Hueso Alveolar/genética , Pérdida de Hueso Alveolar/metabolismo , Pérdida de Hueso Alveolar/patología , Proceso Alveolar/patología , Animales , Estudios de Casos y Controles , Periodontitis Crónica/genética , Periodontitis Crónica/metabolismo , Periodontitis Crónica/patología , Modelos Animales de Enfermedad , Humanos , Vasos Linfáticos/patología , Masculino , Maxilar/patología , Ratones Endogámicos C57BL , Ratones Transgénicos , Osteoclastos/metabolismo , Osteoclastos/patología , Factor de Necrosis Tumoral alfa/genética
8.
Braz Oral Res ; 34: e016, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32130363

RESUMEN

Horizontal bone loss after tooth extraction is a common finding that demands bone reconstruction in various cases. The aim of this study was to assess the horizontal alveolar status in partially and completely edentulous patients using cone-beam computed tomography (CBCT). In total, 1516 CBCT scans of 1404 adult patients were analyzed. Assessment of the images was performed in accordance with the previously published horizontal alveolar change (HAC) classification, which categorizes horizontal bone defects into four classes: HAC 1, HAC 2, HAC 3 and HAC 4 (from the least severe to the most severe condition). Analysis of 1048 scans from partially edentulous patients presented a distribution of 63.55%, 22.14%, 13.36% and 0.95% in HAC 1, HAC 2, HAC 3 and HAC 4, respectively. Analysis of 468 scans from completely edentulous patient images presented a distribution of 19.87%, 28.63%, 41.67% and 9.83% in HAC 1, HAC 2, HAC 3 and HAC 4, respectively. Based on these results, as in HAC 4, no cancellous bone was found between the cortical buccal and lingual/palatal bone plates, it seems reasonable to state that the absence of cancellous bone is higher in completely edentulous patients than in partially edentulous patients. Therefore, the absence of cancellous bone seems to be higher in completely edentulous than in partially edentulous patients.


Asunto(s)
Pérdida de Hueso Alveolar/epidemiología , Pérdida de Hueso Alveolar/patología , Proceso Alveolar/patología , Boca Edéntula/epidemiología , Boca Edéntula/patología , Adolescente , Adulto , Anciano , Pérdida de Hueso Alveolar/diagnóstico por imagen , Proceso Alveolar/diagnóstico por imagen , Aumento de la Cresta Alveolar , Brasil/epidemiología , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/patología , Tomografía Computarizada de Haz Cónico/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Boca Edéntula/diagnóstico por imagen , Prevalencia , Estudios Retrospectivos , Adulto Joven
9.
Cell Prolif ; 53(4): e12800, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32215984

RESUMEN

OBJECTIVES: The aim of this study was to investigate the role of p75 neurotrophin receptor (p75NTR) in regulating the mouse alveolar bone development and the mineralization potential of murine ectomesenchymal stem cells (EMSCs). Moreover, we tried to explore the underlying mechanisms associated with the PI3K/Akt/ß-catenin pathway. MATERIALS AND METHODS: p75NTR knockout (p75NTR-/- ) mice and wild-type (WT) littermates were used. E12.5d p75NTR-/- and WT EMSCs were isolated in the same pregnant p75NTR-/+ mice from embryonic maxillofacial processes separately. Mouse alveolar bone mass was evaluated using micro-CT. Differential osteogenic differentiation pathways between p75NTR-/- and WT EMSCs were analysed by RNA-sequencing. The PI3K inhibitor LY294002 and PI3K agonist 740Y-P were used to regulate the PI3K/Akt pathway in EMSCs. p75NTR overexpression lentiviruses, p75NTR knock-down lentiviruses and recombined mouse NGF were used to transfect cells. RESULTS: The alveolar bone mass was found reduced in the p75NTR knockout mouse comparing to the WT mouse. During mineralization induction, p75NTR-/- EMSCs displayed decreased osteogenic capacity and downregulated PI3K/Akt/ß-catenin signalling. The PI3K/Akt/ß-catenin pathway positively regulates the potential of differential mineralization in EMSCs. The promotive effect of p75NTR overexpression can be attenuated by LY294002, while the inhibitory effect of p75NTR knock-down on Runx2 and Col1 expression can be reversed by 740Y-P. CONCLUSION: Deletion of p75NTR reduced alveolar bone mass in mice. P75NTR positively regulated the osteogenic differentiation of EMSCs via enhancing the PI3K/Akt/ß-catenin pathway.


Asunto(s)
Pérdida de Hueso Alveolar/genética , Enfermedades Mandibulares/genética , Receptores de Factor de Crecimiento Nervioso/genética , Transducción de Señal , Pérdida de Hueso Alveolar/metabolismo , Pérdida de Hueso Alveolar/patología , Animales , Células Cultivadas , Eliminación de Gen , Masculino , Enfermedades Mandibulares/metabolismo , Enfermedades Mandibulares/patología , Ratones , Ratones Noqueados , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores de Factor de Crecimiento Nervioso/metabolismo , beta Catenina/metabolismo
10.
Braz Oral Res ; 34: e012, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32049112

RESUMEN

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.


Asunto(s)
Lipopéptidos/farmacología , Periodontitis/etiología , Periodontitis/patología , Receptor Toll-Like 2/antagonistas & inhibidores , Pérdida de Hueso Alveolar/etiología , Pérdida de Hueso Alveolar/patología , Proceso Alveolar/efectos de los fármacos , Proceso Alveolar/patología , Animales , Modelos Animales de Enfermedad , Encía/efectos de los fármacos , Encía/patología , Gingivitis/etiología , Gingivitis/patología , Masculino , Ratones Endogámicos C57BL , Osteoclastos/efectos de los fármacos , Osteoclastos/fisiología , Periodontitis/microbiología , Distribución Aleatoria , Fosfatasa Ácida Tartratorresistente , Factores de Tiempo , Microtomografía por Rayos X
11.
J Appl Oral Sci ; 28: e20190140, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31800874

RESUMEN

OBJECTIVE: The goal of the present study was to determine the effect of systemic and topical ozone application on alveolar bone loss (ABL) by evaluating the effect of Hypoxia-inducible factor -1 alpha (HIF-1-α) and receptor activator of NF-kB ligand (RANKL)-positive cells on histopathological and immunohistochemical changes in a rat periodontitis model. METHODOLOGY: Thirty male Wistar rats were divided into three groups: 1) Group C (control group); 2) Group SO (systemic ozone group) and 3) Group TO (topical ozone group). Experimental periodontitis was induced with a 3/0 silk suture placed at the mandibular left first molars of rats, and the suture was removed 14 days later. Ozone gas was injected intraperitoneally (0.7 mg/kg) in SO group. Topical ozone application protocol was performed using an ozone generator at 80% concentration (4th grade) 90- degree probe for the duration of 30 s. Both ozone applications were carried out for two weeks at intervals of two days. Histomorphometric and immunohistochemical analysis were performed. RESULTS: ABL was significantly lower in Group SO compared to Group C (p: 0.0052). HIF-1α- positive cells were significantly lower in Group TO than in Group C (p: 0.0043). RANKL-positive cells were significantly lower in Group SO and in Group TO compared to the control group (p: 0.0033, p: 0.0075, respectively). CONCLUSION: Both ozone applications decreased RANKL-positive cell counts, TO application decreased HIF-1-α positive cells counts, and SO application was found to be more effective in reducing ABL compared to control group.


Asunto(s)
Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/análisis , Ozono/administración & dosificación , Periodontitis/tratamiento farmacológico , Periodontitis/patología , Administración Tópica , Animales , Recuento de Células , Inmunohistoquímica , Masculino , Ligando RANK/análisis , Ratas Wistar , Reproducibilidad de los Resultados , Resultado del Tratamiento
12.
Inflammation ; 43(1): 220-230, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31720989

RESUMEN

Periodontitis is an inflammation characterized by alveolar bone resorption caused by imbalance in bone homeostasis. It is known that autophagy is related to inflammation and bone metabolism. However, whether autophagy inhibitors could be used for periodontitis in animal models remains unknown. We investigated the role of two classical autophagy inhibitors, 3-methyladenine (3-MA) and chloroquine (CQ), on the development of rat experimental periodontitis in terms of the bone loss (micro-CT), the number of inflammatory cells (hematoxylin and eosin staining), and the osteoclastic activity (tartrate-resistant acid phosphatase staining). Expression of autophagy-related genes and nuclear factor kappa B p65 (NF-κB p65) were assessed by immunohistochemistry. Expression of Beclin-1 and microtubule-associated proteins 1A/1B light chain 3 (LC3) were analyzed by Western blot. To further observe the effect of autophagy inhibitors on osteoclasts (OCs) in vitro, bone marrow-derived mononuclear macrophages were used. Together, these findings indicated that topical administration of 3-MA or CQ reduced the infiltration of inflammatory cells and alveolar bone resorption in experimental periodontitis. Furthermore, 3-MA and CQ may attenuate activation of OCs by autophagy. Therefore, 3MA and CQ may have prophylactic and therapeutic potential for inflammation and alveolar bone resorption in periodontitis in the future.


Asunto(s)
Adenina/análogos & derivados , Pérdida de Hueso Alveolar/prevención & control , Proceso Alveolar/efectos de los fármacos , Antiinflamatorios/farmacología , Autofagia/efectos de los fármacos , Cloroquina/farmacología , Osteoclastos/efectos de los fármacos , Periodontitis/prevención & control , Adenina/farmacología , Pérdida de Hueso Alveolar/metabolismo , Pérdida de Hueso Alveolar/microbiología , Pérdida de Hueso Alveolar/patología , Proceso Alveolar/metabolismo , Proceso Alveolar/microbiología , Proceso Alveolar/patología , Animales , Proteínas Relacionadas con la Autofagia/metabolismo , Células Cultivadas , Modelos Animales de Enfermedad , Masculino , Osteoclastos/metabolismo , Osteoclastos/microbiología , Osteoclastos/patología , Osteogénesis/efectos de los fármacos , Periodontitis/metabolismo , Periodontitis/microbiología , Periodontitis/patología , Porphyromonas gingivalis , Ratas Sprague-Dawley , Factor de Transcripción ReIA/metabolismo
13.
J Periodontal Res ; 55(1): 107-115, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31552683

RESUMEN

BACKGROUND AND OBJECTIVE: Periodontal disease (PD) afflicts approximately 50% of the population in the United States and is characterized by chronic inflammation of the periodontium that can lead to loss of the periodontal ligament through collagen degradation, loss of alveolar bone, and to eventual tooth loss. Previous studies have implicated transglutaminase (TG) activity in promoting thin collagen I fiber morphology and decreased mechanical strength in homeostatic PDL. The aim of this study was to determine whether TG activity influenced collagen assembly in PDL in the setting of periodontal disease. MATERIAL AND METHODS: A ligature model was used to induce clinically relevant PD in mice. Mice with ligature were assessed at 5 and 14 days to determine PDL collagen morphology, transglutaminase (TG) activity, and bone loss. The effects of inhibition of TG on PDL were assessed by immunohistochemistry and second-harmonic generation (SHG) to visualize collagen fibers in native tissue. RESULTS: Ligature placement around the 2nd molar resulted in significant bone loss and a decrease in total collagen content after 5 days of ligature placement. A significant increase in thin over thick fibers was also demonstrated in mice with ligature at 5 days associated with apparent increases in immunoreactivity for TG2 and for TG-mediated N-ε-γ-glutamyl cross-links in PDL. Inhibition of TG activity increased total collagen and thick collagen fiber content over vehicle control in mice with ligature for 5 days. SHG of PDL was used to visualize and quantify the effects of TG inhibition on enhanced collagen fiber organization in unfixed control and diseased PDL. CONCLUSION: These studies support a role of TG in regulating collagen fiber assembly and suggest that strategies to inhibit TG activity in disease might contribute to restoration of PDL tissue integrity.


Asunto(s)
Colágeno/metabolismo , Ligamento Periodontal/enzimología , Periodontitis/enzimología , Transglutaminasas/antagonistas & inhibidores , Pérdida de Hueso Alveolar/patología , Aminas/farmacología , Animales , Biotina/análogos & derivados , Biotina/farmacología , Diferenciación Celular , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Distribución Aleatoria , Microtomografía por Rayos X
14.
J Periodontal Res ; 55(2): 191-198, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31541471

RESUMEN

BACKGROUND AND OBJECTIVE: Periodontitis is a prevalent oral disease responsible for tooth loss. MicroRNAs have been proven crucial in bone disorders over the past decades. Promotive effect on osteogenic activities by microRNA-335-5p (miR-335-5p) has been well demonstrated, but its role involved in the pathogenesis of periodontitis remains elusive. In this study, we established experimental periodontitis (EP) on transgenic mice overexpressing miR-335-5p (335-Tg) to investigate the novel effects of miR-335-5p on periodontal inflammation and bone loss. METHODS: Experimental periodontitis was established via ligation. The expression of inflammatory and osteoclastic genes was examined by quantitative real-time PCR (qPCR). Morphology of alveolar bone was analyzed by microcomputed tomography (µCT). Hematoxylin and eosin (H&E), tartrate-resistant acid phosphatase (TRAP), and Toll-like receptor 4 (TLR4) immunohistochemistry (IHC) staining were conducted for histological analysis. RESULTS: The expression of miR-335-5p decreased significantly in the periodontal tissues of EP. Compared to the WT-EP group, µCT analysis showed less bone loss in the 335-Tg-EP group accompanying with a decreased number of TRAP-positive osteoclasts. H&E and IHC staining exhibited attenuated inflammation and TLR4 expression in the 335-Tg-EP group. Furthermore, reduced expressions of IL-1ß, IL-6, TNF-α, and TLR4 were also detected in the 335-Tg-EP group. Overexpression of miR-335-5p in vivo weakened the periodontal bone destruction and inflammation compared with the WT-EP group. CONCLUSIONS: Our data exhibit novel roles of miR-335-5p in preventing bone loss and inflammation in experimental periodontitis.


Asunto(s)
Pérdida de Hueso Alveolar/patología , MicroARNs/genética , Periodontitis/patología , Pérdida de Hueso Alveolar/diagnóstico por imagen , Animales , Citocinas/metabolismo , Ratones , Ratones Transgénicos , Osteoclastos/citología , Receptor Toll-Like 4/metabolismo , Microtomografía por Rayos X
15.
J. appl. oral sci ; 28: e20190140, 2020. tab, graf
Artículo en Inglés | LILACS, BBO - Odontología | ID: biblio-1090777

RESUMEN

Abstract Objective: The goal of the present study was to determine the effect of systemic and topical ozone application on alveolar bone loss (ABL) by evaluating the effect of Hypoxia-inducible factor −1 alpha (HIF-1-α) and receptor activator of NF-kB ligand (RANKL)-positive cells on histopathological and immunohistochemical changes in a rat periodontitis model. Methodology: Thirty male Wistar rats were divided into three groups: 1) Group C (control group); 2) Group SO (systemic ozone group) and 3) Group TO (topical ozone group). Experimental periodontitis was induced with a 3/0 silk suture placed at the mandibular left first molars of rats, and the suture was removed 14 days later. Ozone gas was injected intraperitoneally (0.7 mg/kg) in SO group. Topical ozone application protocol was performed using an ozone generator at 80% concentration (4th grade) 90- degree probe for the duration of 30 s. Both ozone applications were carried out for two weeks at intervals of two days. Histomorphometric and immunohistochemical analysis were performed. Results: ABL was significantly lower in Group SO compared to Group C (p: 0.0052). HIF-1α- positive cells were significantly lower in Group TO than in Group C (p: 0.0043). RANKL-positive cells were significantly lower in Group SO and in Group TO compared to the control group (p: 0.0033, p: 0.0075, respectively). Conclusion: Both ozone applications decreased RANKL-positive cell counts, TO application decreased HIF-1-α positive cells counts, and SO application was found to be more effective in reducing ABL compared to control group.


Asunto(s)
Animales , Masculino , Ozono/administración & dosificación , Periodontitis/patología , Periodontitis/tratamiento farmacológico , Pérdida de Hueso Alveolar/patología , Pérdida de Hueso Alveolar/tratamiento farmacológico , Subunidad alfa del Factor 1 Inducible por Hipoxia/análisis , Inmunohistoquímica , Recuento de Células , Reproducibilidad de los Resultados , Administración Tópica , Resultado del Tratamiento , Ratas Wistar , Ligando RANK/análisis
16.
J. appl. oral sci ; 28: e20190140, 2020. tab, graf
Artículo en Inglés | LILACS, BBO - Odontología | ID: biblio-1056590

RESUMEN

Abstract Objective: The goal of the present study was to determine the effect of systemic and topical ozone application on alveolar bone loss (ABL) by evaluating the effect of Hypoxia-inducible factor −1 alpha (HIF-1-α) and receptor activator of NF-kB ligand (RANKL)-positive cells on histopathological and immunohistochemical changes in a rat periodontitis model. Methodology: Thirty male Wistar rats were divided into three groups: 1) Group C (control group); 2) Group SO (systemic ozone group) and 3) Group TO (topical ozone group). Experimental periodontitis was induced with a 3/0 silk suture placed at the mandibular left first molars of rats, and the suture was removed 14 days later. Ozone gas was injected intraperitoneally (0.7 mg/kg) in SO group. Topical ozone application protocol was performed using an ozone generator at 80% concentration (4th grade) 90- degree probe for the duration of 30 s. Both ozone applications were carried out for two weeks at intervals of two days. Histomorphometric and immunohistochemical analysis were performed. Results: ABL was significantly lower in Group SO compared to Group C (p: 0.0052). HIF-1α- positive cells were significantly lower in Group TO than in Group C (p: 0.0043). RANKL-positive cells were significantly lower in Group SO and in Group TO compared to the control group (p: 0.0033, p: 0.0075, respectively). Conclusion: Both ozone applications decreased RANKL-positive cell counts, TO application decreased HIF-1-α positive cells counts, and SO application was found to be more effective in reducing ABL compared to control group.


Asunto(s)
Animales , Masculino , Ozono/administración & dosificación , Periodontitis/patología , Periodontitis/tratamiento farmacológico , Pérdida de Hueso Alveolar/patología , Pérdida de Hueso Alveolar/tratamiento farmacológico , Subunidad alfa del Factor 1 Inducible por Hipoxia/análisis , Inmunohistoquímica , Recuento de Células , Reproducibilidad de los Resultados , Administración Tópica , Resultado del Tratamiento , Ratas Wistar
17.
Sci Rep ; 9(1): 19257, 2019 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-31848404

RESUMEN

Periodontitis is a prevalent chronic inflammatory disease due to the host response (IL-1ß, IL-6, TNF-α and IL-17A) to oral bacteria such as Porphyromonas gingivalis. The newer members of the IL-1 family, IL-36s (IL-36α/IL-36ß/IL-36γ/IL-36Ra/IL-38) are known to be involved in host defense against P. gingivalis in oral epithelial cells (OECs) and are considered as key inflammatory mediators in chronic diseases. The aim of this study was to investigate the potential role of IL-36s in periodontitis. We showed here that IL-36γ mRNA gingival expression is higher in periodontitis patients, whereas IL-36ß and IL-36Ra mRNA expression are lower compared to healthy controls. Interestingly, the elevated IL-36γ expression in patients is positively correlated with the RANKL/OPG ratio, an index of bone resorption. In vitro, IL-36γ expression was induced through TLR2 activation in primary OECs infected with P. gingivalis but not in gingival fibroblasts, the most widespread cell type in gingival connective tissue. In OECs, recombinant IL-36γ enhanced the expression of inflammatory cytokines (IL-1ß, IL-6, TNF-α and IL-36γ), of TLR2 and importantly, the RANKL/OPG ratio. These findings suggest that IL-36γ could be a pivotal inflammatory player in periodontitis by perpetuating gingival inflammation and its associated alveolar bone resorption and could be a relevant therapeutic target.


Asunto(s)
Pérdida de Hueso Alveolar , Infecciones por Bacteroidaceae , Interleucina-1/metabolismo , Periodontitis , Porphyromonas gingivalis/metabolismo , Pérdida de Hueso Alveolar/metabolismo , Pérdida de Hueso Alveolar/microbiología , Pérdida de Hueso Alveolar/patología , Infecciones por Bacteroidaceae/metabolismo , Infecciones por Bacteroidaceae/patología , Línea Celular , Femenino , Humanos , Inflamación/metabolismo , Inflamación/microbiología , Inflamación/patología , Masculino , Periodontitis/metabolismo , Periodontitis/microbiología , Periodontitis/patología
18.
J Cell Sci ; 133(5)2019 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-31722981

RESUMEN

In periodontal disease (PD), bacterial biofilms cause gingival inflammation, leading to bone loss. In healthy individuals, αvß6 integrin in junctional epithelium maintains anti-inflammatory transforming growth factor-ß1 (TGF-ß1) signaling, whereas its expression is lost in individuals with PD. Bacterial biofilms suppress ß6 integrin expression in cultured gingival epithelial cells (GECs) by attenuating TGF-ß1 signaling, leading to an enhanced pro-inflammatory response. In the present study, we show that GEC exposure to biofilms induced activation of mitogen-activated protein kinases and epidermal growth factor receptor (EGFR). Inhibition of EGFR and ERK stunted both the biofilm-induced ITGB6 suppression and IL1B stimulation. Furthermore, biofilm induced the expression of endogenous EGFR ligands that suppressed ITGB6 and stimulated IL1B expression, indicating that the effects of the biofilm were mediated by autocrine EGFR signaling. Biofilm and EGFR ligands induced inhibitory phosphorylation of the TGF-ß1 signaling mediator Smad3 at S208. Overexpression of a phosphorylation-defective mutant of Smad3 (S208A) reduced the ß6 integrin suppression. Furthermore, inhibition of EGFR signaling significantly reduced bone loss and inflammation in an experimental PD model. Thus, EGFR inhibition may provide a target for clinical therapies to prevent inflammation and bone loss in PD.


Asunto(s)
Pérdida de Hueso Alveolar/patología , Antígenos de Neoplasias/genética , Biopelículas , Células Epiteliales/metabolismo , Receptores ErbB/metabolismo , Encía/citología , Integrinas/genética , Animales , Células Cultivadas , Células Epiteliales/microbiología , Encía/microbiología , Humanos , Mediadores de Inflamación/metabolismo , Ratones , Enfermedades Periodontales/genética , Enfermedades Periodontales/metabolismo , Fosforilación , Transducción de Señal , Factor de Crecimiento Transformador beta1/metabolismo
19.
PLoS One ; 14(11): e0225046, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31710656

RESUMEN

PURPOSE: To compare the longevity and marginal bone loss of narrow-diameter (≤3.3-mm) versus standard-diameter implants supporting single crowns. MATERIAL AND METHODS: The MEDLINE (via PubMed), Scopus, and SciELO databases were searched for relevant publications. In addition, the scientific references provided by each of the implant companies that appeared in the search were reviewed. Intervention studies comparing longevity and bone loss between narrow-diameter and standard-diameter implants were included. RESULTS: The search was limited to in vivo studies in humans. The query returned 1931 results, of which 4 met the inclusion criteria. The implant success rate ranged from 93.8% to 100% over a maximum follow-up of 3 years, with no difference between narrow- and standard-diameter implants. Meta-analysis of all included studies showed greater bone loss in narrow-diameter implants as compared with standard ones; however, when analysis was restricted to randomized trials, no such difference was present. CONCLUSION: The meta-analysis showed no difference in longevity between narrow implants and standard implants when supporting single crowns. However, narrow-diameter implants may be associated with greater marginal bone loss. These findings should be regarded cautiously due to the short follow-up duration and methodological heterogeneity of the primary studies.


Asunto(s)
Pérdida de Hueso Alveolar/patología , Coronas/efectos adversos , Implantes Dentales/efectos adversos , Diseño de Prótesis Dental , Adulto , Humanos , Persona de Mediana Edad , Sesgo de Publicación , Ensayos Clínicos Controlados Aleatorios como Asunto , Riesgo , Adulto Joven
20.
Braz Oral Res ; 33(suppl 1): e073, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31576957

RESUMEN

Soft tissue defects around dental implants, such as papilla or volume loss, peri-implant recession and alterations of the ridge color and/or texture, lead to esthetic and functional complaints. Treatments of these defects in implants are more demanding than in teeth because peri-implant tissue exhibits different anatomical and histological characteristics. This narrative review discusses the proposed treatments for soft tissue defects around implants in the current literature. Several clinical and pre-clinical studies addressed methods to augment the quantity of the peri-implant keratinized mucosa. Autogenous grafts performed better than soft tissue substitutes in the treatment of soft tissue defects, but there is no clinical consensus on the more appropriate donor area for connective tissue grafts. Treatment for facial volume loss, alterations on the mucosa color or texture and shallow peri-implant recessions are more predictable than deep recessions and sites that present loss of papilla. Correction of peri-implant soft tissue defects may be challenging, especially in areas that exhibit larger defects and interproximal loss. Therefore, the regeneration of soft and hard tissues during implant treatment is important to prevent the occurrence of these alterations.


Asunto(s)
Pérdida de Hueso Alveolar/terapia , Prótesis Anclada al Hueso/efectos adversos , Interfase Hueso-Implante , Implantes Dentales/efectos adversos , Recesión Gingival/terapia , Pérdida de Hueso Alveolar/etiología , Pérdida de Hueso Alveolar/patología , Interfase Hueso-Implante/patología , Cara/patología , Recesión Gingival/etiología , Recesión Gingival/patología , Humanos , Reproducibilidad de los Resultados , Resultado del Tratamiento
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