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1.
J Oral Maxillofac Surg ; 73(4): 745-58, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25661502

RESUMO

PURPOSE: This study tested the use of a dentate transport segment for the reconstruction of a large U-shaped defect in the anterior segment of the canine mandible using a novel curved reconstruction plate. The quality and quantity of bone regenerate formed by dentate versus edentulous transport segments were compared. MATERIALS AND METHODS: In 5 adult foxhound dogs, a defect of 70 to 75 mm was created in the canine mandible by excising the mandible anterior to the right and left fourth premolars. Reconstruction was performed by trifocal distraction osteogenesis using a bone transport reconstruction plate (BTRP-02), with 2 transport units being activated simultaneously, one on either side of the defect, 1 dentate and 1 edentulous. Bilateral distraction proceeded at a rate of 1 mm/day until the segments docked against each other in the midline. After 39 to 44 days of consolidation, the animals were euthanized. The quantity and quality of bone regeneration on the 2 sides were compared using micro-computed tomography. RESULTS: The defect reconstruction was successful. The amount and quality of bone formed by the transport segments were similar on the 2 sides. There were no major differences in the bone volume fraction and density of the regenerate bone formed by the 2 transport segments. The bone volume fraction and density of the regenerate bone were considerably lower than those of the host bone in the distal segments, likely owing to the short consolidation period. CONCLUSIONS: Bone transport remains a viable option in reconstructing anterior segmental defects in the mandible. The use of dentate or edentulous transport segments for reconstruction provides options for the surgeon in often highly compromised patients requiring these surgeries.


Assuntos
Doenças Mandibulares/cirurgia , Osteogênese por Distração/métodos , Procedimentos de Cirurgia Plástica/métodos , Animais , Materiais Biocompatíveis/química , Densidade Óssea/fisiologia , Placas Ósseas , Regeneração Óssea/fisiologia , Tomografia Computadorizada de Feixe Cônico/métodos , Arco Dental/cirurgia , Dentição , Cães , Desenho de Equipamento , Estudos de Viabilidade , Tecido de Granulação/patologia , Imageamento Tridimensional/métodos , Arcada Edêntula/cirurgia , Masculino , Mandíbula/cirurgia , Tamanho do Órgão , Osteogênese por Distração/instrumentação , Procedimentos de Cirurgia Plástica/instrumentação , Titânio/química , Microtomografia por Raio-X/métodos
2.
Infect Immun ; 82(1): 101-11, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24126519

RESUMO

Several intracellular pathogens, including a key etiological agent of chronic periodontitis, Porphyromonas gingivalis, infect blood myeloid dendritic cells (mDCs). This infection results in pathogen dissemination to distant inflammatory sites (i.e., pathogen trafficking). The alteration in chemokine-chemokine receptor expression that contributes to this pathogen trafficking function, particularly toward sites of neovascularization in humans, is unclear. To investigate this, we utilized human monocyte-derived DCs (MoDCs) and primary endothelial cells in vitro, combined with ex vivo-isolated blood mDCs and serum from chronic periodontitis subjects and healthy controls. Our results, using conditional fimbria mutants of P. gingivalis, show that P. gingivalis infection of MoDCs induces an angiogenic migratory profile. This profile is enhanced by expression of DC-SIGN on MoDCs and minor mfa-1 fimbriae on P. gingivalis and is evidenced by robust upregulation of CXCR4, but not secondary lymphoid organ (SLO)-homing CCR7. This disruption of SLO-homing capacity in response to respective chemokines closely matches surface expression of CXCR4 and CCR7 and is consistent with directed MoDC migration through an endothelial monolayer. Ex vivo-isolated mDCs from the blood of chronic periodontitis subjects, but not healthy controls, expressed a similar migratory profile; moreover, sera from chronic periodontitis subjects expressed elevated levels of CXCL12. Overall, we conclude that P. gingivalis actively "commandeers" DCs by reprogramming the chemokine receptor profile, thus disrupting SLO homing, while driving migration toward inflammatory vascular sites.


Assuntos
Infecções por Bacteroidaceae/metabolismo , Movimento Celular/fisiologia , Periodontite Crônica/metabolismo , Células Dendríticas/microbiologia , Células Mieloides/microbiologia , Porphyromonas gingivalis/fisiologia , Receptores de Quimiocinas/metabolismo , Infecções por Bacteroidaceae/imunologia , Infecções por Bacteroidaceae/microbiologia , Estudos de Casos e Controles , Moléculas de Adesão Celular/metabolismo , Quimiocina CXCL12/metabolismo , Quimiotaxia/fisiologia , Periodontite Crônica/imunologia , Periodontite Crônica/microbiologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Endoteliais/metabolismo , Fímbrias Bacterianas/genética , Fímbrias Bacterianas/fisiologia , Humanos , Lectinas Tipo C/metabolismo , Lipopolissacarídeos/farmacologia , Células Mieloides/efeitos dos fármacos , Células Mieloides/imunologia , Células Mieloides/metabolismo , Neovascularização Patológica/microbiologia , Fenótipo , Receptores CCR7/metabolismo , Receptores CXCR4/metabolismo , Receptores de Superfície Celular/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
3.
Implant Dent ; 23(3): 319-27, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24776941

RESUMO

PURPOSE: To investigate the effects of hyperglycemia and metformin (a popular biguanide antidiabetic) on periimplant healing. METHODS: Thirty-six male rats were assigned to 3 groups: (1) nondiabetic Wistar-Kyoto rats (controls), (2) Goto-Kakizaki (GK) spontaneously diabetic rats (GK group), and (3) GK rats were fed metformin (100 mg/kg body weight per day) in their water for 4 weeks (GK + Met group). The right maxillary first molars were extracted and sites were allowed 1 month to heal. Titanium implants (1 × 3 mm) were placed in healed extraction sites. Six rats from each group were analyzed at weeks 1 and 4 by micro computed tomography for bone/implant contact ratio, percent bone volume, trabecular number, and bone mineral density. Blood was also analyzed for glucose, HbA1c, and pyridinoline (PYD). RESULTS: At week 1, glucose levels in the GK-Met rats were high, and all bone parameters were similar to GK rats (lower bone parameters and higher PYD than controls). At week 4, glucose levels in the GK-Met rats and all parameters were similar to controls. CONCLUSIONS: Hyperglycemic GK type 2 diabetic rats showed improved blood glucose and wound healing around oral implants after metformin administration.


Assuntos
Implantes Dentários/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Extração Dentária/efeitos adversos , Cicatrização/efeitos dos fármacos , Animais , Glicemia/análise , Glicemia/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Remodelação Óssea/fisiologia , Modelos Animais de Doenças , Masculino , Ratos , Ratos Endogâmicos , Ratos Endogâmicos WKY , Microtomografia por Raio-X
4.
Exp Mol Pathol ; 95(3): 298-306, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23999113

RESUMO

A number of studies have revealed that Type I diabetes (T1D) is associated with bone loss and an increased risk of fractures. T1D induces oxidative stress in various tissues and organs. Vitamin C plays an important role in the attenuation of oxidative stress; however, little is known about the effect of T1D induced oxidative stress on the regulation of vitamin C transporter in bone and bone marrow cells. To investigate this, T1D was induced in mice by multiple low dose injections of streptozotocin. We have demonstrated that endogenous antioxidants, glutathione peroxidase (GPx) and superoxide dismutase (SOD) are down-regulated in the bone and bone marrow of T1D. The vitamin C transporter isoform SVCT2, the only known transporter expressed in bone and bone marrow stromal cells (BMSCs), is negatively regulated in the bone and bone marrow of T1D. The µCT imaging of the bone showed significantly lower bone quality in the 8 week T1D mouse. The in-vitro study in BMSCS showed that the knockdown of SVCT2 transporter decreases ascorbic acid (AA) uptake, and increases oxidative stress. The significant reversing effect of antioxidant vitamin C is only possible in control cells, not in knockdown cells. This study suggested that T1D induces oxidative stress and decreases SVCT2 expression in the bone and bone marrow environment. Furthermore, this study confirms that T1D increases bone resorption, decreases bone formation and changes the microstructure of bones. This study has provided evidence that the regulation of the SVCT2 transporter plays an important role not only in T1D osteoporosis but also in other oxidative stress-related musculoskeletal complications.


Assuntos
Medula Óssea/patologia , Osso e Ossos/patologia , Diabetes Mellitus Experimental/patologia , Regulação da Expressão Gênica , Estresse Oxidativo , Transportadores de Sódio Acoplados à Vitamina C/metabolismo , Animais , Western Blotting , Medula Óssea/metabolismo , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Osso e Ossos/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Técnicas Imunoenzimáticas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transportadores de Sódio Acoplados à Vitamina C/antagonistas & inibidores , Transportadores de Sódio Acoplados à Vitamina C/genética , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
5.
J Oral Maxillofac Surg ; 71(6): 1107-18, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23477871

RESUMO

PURPOSE: To compare the efficiency of recombinant human bone morphogenetic protein 2 (rhBMP2)/absorbable collagen sponge (ACS) in the delayed versus immediate reconstruction of mandibular segmental defects in a canine model. METHODS: We randomized 11 dogs into 2 groups: immediate reconstruction (group 1, n = 6) and delayed reconstruction (group 2, n = 5). A 35-mm osteoperiosteal segmental defect was created on the left side of the mandible. Reconstruction with rhBMP2/ACS was carried out in the same setting in group 1 or at 4 weeks postoperatively in group 2. The contralateral side acted as an internal control. Animals were monitored both clinically and radiographically throughout the experiment. Twelve weeks after the application of rhBMP2/ACS, the quantity of bone formation was evaluated using regenerate mapping and histomorphometric analysis. Qualitative evaluation was performed based on bone mineral density and Vickers microhardness (µHV) testing. RESULTS: Postoperative seromas were observed in 83.3% of group 1 dogs only. Group 1 showed significantly larger physical dimensions than group 2 in most regenerate zones. Successful regeneration was achieved in 83.3% of group 1 dogs (discontinuity defect was seen in 1 of 6 dogs in group 1). Meanwhile, none of the 5 dogs in group 2 could be considered to have undergone successful regeneration (3 dogs had discontinuity defects, bony union occurred only in the basal third in the fourth dog, and the last dog showed union with only a shell of bone). The percent bone area and percent defect filling were significantly higher in group 1 than in group 2 (percent bone area, 52.4% ± 5.6% in group 1 and 36.6% ± 11.2% in group 2 [P = .02]; percent defect filling, 56.3% ± 5.5% in group 1 and 38.5% ± 10.8% in group 2 [P = .01]). Group 1 showed higher bone mineral density (0.7 ± 0.3 mg/cm(3) in group 1 and 0.4 ± 0.1 mg/cm(3) in group 2, P = .1). Finally, µHV was significantly higher in group 1 (20.3 ± 2.6 µHV) than in group 2 (13.2 ± 2.4 µHV) (P = .01). CONCLUSIONS: Delaying the application of rhBMP2/ACS for 4 weeks attenuated the quantity and quality of regenerated bone in mandibular segmental defects.


Assuntos
Proteína Morfogenética Óssea 2/administração & dosagem , Regeneração Óssea/efeitos dos fármacos , Portadores de Fármacos , Regeneração Tecidual Guiada/métodos , Mandíbula/cirurgia , Animais , Densidade Óssea/efeitos dos fármacos , Colágeno , Cães , Dureza/efeitos dos fármacos , Humanos , Distribuição Aleatória , Proteínas Recombinantes/administração & dosagem , Fatores de Tempo
6.
BMC Cancer ; 12: 203, 2012 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-22642622

RESUMO

BACKGROUND: Abnormal NF-κB2 activation has been implicated in the pathogenesis of multiple myeloma, a cancer of plasma cells. However, a causal role for aberrant NF-κB2 signaling in the development of plasma cell tumors has not been established. Also unclear is the molecular mechanism that drives the tumorigenic process. We investigated these questions by using a transgenic mouse model with lymphocyte-targeted expression of p80HT, a lymphoma-associated NF-κB2 mutant, and human multiple myeloma cell lines. METHODS: We conducted a detailed histopathological characterization of lymphomas developed in p80HT transgenic mice and microarray gene expression profiling of p80HT B cells with the goal of identifying genes that drive plasma cell tumor development. We further verified the significance of our findings in human multiple myeloma cell lines. RESULTS: Approximately 40% of p80HT mice showed elevated levels of monoclonal immunoglobulin (M-protein) in the serum and developed plasma cell tumors. Some of these mice displayed key features of human multiple myeloma with accumulation of plasma cells in the bone marrow, osteolytic bone lesions and/or diffuse osteoporosis. Gene expression profiling of B cells from M-protein-positive p80HT mice revealed aberrant expression of genes known to be important in the pathogenesis of multiple myeloma, including cyclin D1, cyclin D2, Blimp1, survivin, IL-10 and IL-15. In vitro assays demonstrated a critical role of Stat3, a key downstream component of IL-10 signaling, in the survival of human multiple myeloma cells. CONCLUSIONS: These findings provide a mouse model for human multiple myeloma with aberrant NF-κB2 activation and suggest a molecular mechanism for NF-κB2 signaling in the pathogenesis of plasma cell tumors by coordinated regulation of plasma cell generation, proliferation and survival.


Assuntos
Diferenciação Celular/genética , Mutação , Subunidade p52 de NF-kappa B/genética , Plasmocitoma/genética , Transdução de Sinais , Animais , Proteínas Sanguíneas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Transgênicos , Subunidade p52 de NF-kappa B/metabolismo , Plasmocitoma/metabolismo , Plasmocitoma/patologia , Fator de Transcrição STAT3/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
7.
Exp Mol Pathol ; 92(1): 54-8, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21983138

RESUMO

Hallmark features of type 2 diabetes mellitus include glucosuria and polyuria. Further, renal aquaporin 2 is pivotal to regulation of fluid excretion and urine osmolality. Accordingly, we tested the hypothesis that the db/db mouse displays increased glucosuria and fluid excretion but reduced urine osmolality in association with decreased renal aquaporin 2 level. In addition, we examined the effect of chromium picolinate (Cr(pic)3) which is purported to improve glycemic control. The db/db mice excreted more urine in association with marked glucose excretion but lower urine osmolality than db/m control group. Light microscopic examination of renal tissue revealed proliferation of tubular structures in db/db compared to the db/m mice, a feature validated with Ki67 immunostaining. Further, these tubules showed generally similar immunostaining intensity and pattern for aquaporin 2 indicating that proliferated tubules are of distal origin. On the other hand, renal aquaporin 2 protein level was significantly higher in the db/db than db/m group. Treatment of db/db mice with Cr(pic)3 reduced plasma glucose and hemoglobin A1c (~15-17%, p<0.05) and Ki67 positive cells but other parameters were similar to their untreated counterparts. Collectively, these findings suggest that proliferation of renal distal tubules and increased aquaporin 2 level likely represent an adaptive mechanism to regulate fluid excretion to prevent dehydration in the setting of marked glucosuria in the db/db mouse, features not affected by Cr(pic)3 treatment. These observations are of relevance to increasing interest in developing therapeutic agents that facilitate renal glucose elimination.


Assuntos
Aquaporina 2/urina , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Túbulos Renais Distais/patologia , Ácidos Picolínicos/administração & dosagem , Animais , Transporte Biológico/efeitos dos fármacos , Glicemia/análise , Peso Corporal/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Desidratação/prevenção & controle , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/urina , Modelos Animais de Doenças , Índice Glicêmico/efeitos dos fármacos , Glicosúria , Insulina/sangue , Antígeno Ki-67/análise , Antígeno Ki-67/efeitos dos fármacos , Masculino , Camundongos , Concentração Osmolar , Poliúria/urina , Distribuição Aleatória
8.
J Oral Maxillofac Surg ; 70(2): 429-39, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21601342

RESUMO

PURPOSE: Bone transport distraction osteogenesis provides a promising alternative to traditional grafting techniques. However, existing bone transport distraction osteogenesis devices have many limitations. The purpose of this research was to test a new device, the mandibular bone transport reconstruction plate, in an animal model with comparable mandible size to humans and to histologically and mechanically examine the regenerate bone. MATERIALS AND METHODS: Eleven adult foxhounds were divided into an unreconstructed control group of 5 animals and an experimental group of 6 animals. In each animal, a 34-mm segmental defect was created in the mandible. The defect was reconstructed with a bone transport reconstruction plate. Histologic and biomechanical characteristics of the regenerate and unrepaired defect were analyzed and compared with bone on the contralateral side of the mandible after 4 weeks of consolidation. RESULTS: The reconstructed defect was bridged with new bone, with little bone in the control defect. Regenerate density and microhardness were 22.3% and 42.6%, respectively, lower than the contralateral normal bone. Likewise, the anisotropy of the experimental group was statistically lower than in the contralateral bone. Half the experimental animals showed nonunion at the docking site. CONCLUSION: The device was very stable and easy to install and activate. After 1 month of consolidation, the defect was bridged with new bone, with evidence of active bone formation. Regenerate bone was less mature than the control bone. Studies are underway to identify when the regenerate properties compare with normal bone and to identify methods to augment bone union at the docking site.


Assuntos
Regeneração Óssea/fisiologia , Mandíbula/cirurgia , Osteogênese por Distração/métodos , Animais , Anisotropia , Fenômenos Biomecânicos , Densidade Óssea/fisiologia , Placas Ósseas , Parafusos Ósseos , Corantes , Cães , Módulo de Elasticidade , Desenho de Equipamento , Dureza , Mandíbula/diagnóstico por imagem , Mandíbula/patologia , Modelos Animais , Osteogênese/fisiologia , Osteogênese por Distração/instrumentação , Osteotomia/métodos , Corantes de Rosanilina , Ultrassonografia , Cicatrização/fisiologia
9.
J Oral Implantol ; 38 Spec No: 511-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21905888

RESUMO

The purpose of this study was to develop a rat model predictive of bisphosphonate-related osteonecrosis of the jaw (BRONJ) after exodontias. Thirty female rats were randomized into 2 groups, control and experimental. The experimental group received 2 intravenous injections of zoledronate (20 µg/kg). The mesial root of the right mandibular first molar was extracted. Rats were euthanized at 0, 4, and 8 weeks. Bone mineral density (BMD), collagen breakdown (pyridinium [PYD]), vascular regeneration (VEGF), and histology were examined. A trend toward higher PYD values was suggested in control vs experimental groups after wounding. Serum VEGF increased significantly after wounding for both control and experimental groups. After 8 weeks, VEGF continued to rise for the experimental group only. In the extraction socket area, BMD was significantly lower after wounding in control vs. zoledronate-treated rats. Histology sections from experimental groups showed bacteria and bone necrosis. Consistent findings of BRONJ features similar to those in humans were observed after zoledronate treatment.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Modelos Animais de Doenças , Imidazóis/efeitos adversos , Alvéolo Dental/efeitos dos fármacos , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/metabolismo , Densidade Óssea/efeitos dos fármacos , Colágeno/efeitos dos fármacos , Colágeno/metabolismo , Feminino , Compostos de Piridínio/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Extração Dentária , Alvéolo Dental/metabolismo , Alvéolo Dental/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/efeitos dos fármacos , Microtomografia por Raio-X , Ácido Zoledrônico
10.
Calcif Tissue Int ; 89(1): 43-52, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21556698

RESUMO

The purpose of this study was to evaluate the structure and material properties of native mandibular bone and those of early regenerate bone, produced by bone transport distraction osteogenesis. Ten adult foxhounds were divided into two groups of five animals each. In all animals, a 3- to 4-cm defect was created on one side of the mandible. A bone transport reconstruction plate, consisting of a reconstruction plate with an attached intraoral transport unit, was utilized to stabilize the mandible and regenerate bone at a rate of 1 mm/day. After the distraction period was finished, the animals were killed at 6 and 12 weeks of consolidation. Micro-computed tomography was used to assess the morphometric and structural indices of regenerate bone and matching bone from the unoperated contralateral side. Significant new bone was formed within the defect in the 6- and 12-week groups. Significant differences (P ≤ 0.05) between mandibular regenerated and native bone were found in regard to bone volume fraction, mineral density, bone surface ratio, trabecular thickness, trabecular separation, and connectivity density, which increased from 12 to 18 weeks of consolidation. We showed that regenerated bone is still mineralizing and that native bone appears denser because of a thick outer layer of cortical bone that is not yet formed in the regenerate. However, the regenerate showed a significantly higher number of thicker trabeculae.


Assuntos
Regeneração Óssea/fisiologia , Mandíbula/fisiologia , Osteogênese por Distração/métodos , Animais , Densidade Óssea/fisiologia , Cães , Mandíbula/anatomia & histologia , Mandíbula/diagnóstico por imagem , Osteogênese/fisiologia , Microtomografia por Raio-X
11.
J Oral Pathol Med ; 40(2): 194-200, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20973827

RESUMO

BACKGROUND: Obesity is a prevalent disorder characterized as marked insulin resistance and low grade inflammation. We tested the hypothesis that obesity upregulates inflammatory markers in the submandibular gland in association with derangements of its architecture and pre-disposition to caries in obese Zucker rats (OZR). We also examined the potential impact of chromium picolinate (Cr(Pic)3), a nutritional supplement suggested to improve glycemic control, on the aforementioned parameters. DESIGN: Male OZR were treated with diets lacking and containing 5 or 10 mg/kg chromium (as Cr(Pic)3) from 6 weeks to about 6 months of age; lean Zucker rats (LZR) served as controls. Thereafter, glycemic status, salivary tissue architecture, and the levels of several inflammatory markers were determined in association with caries susceptibility. RESULTS: OZR showed reduced insulin sensitivity, increased ratio of phospho-nuclear factor-kappa B (NF-κB) to total NF-κB, and increased intercellular adhesion molecule-1 level but similar histological features compared to LZR. Importantly, compared to LZR, OZR displayed rampant caries and a tendency for reduced dentin mineral density. Treatment of OZR with Cr(Pic)3 attenuated upregulation of these proinflammatory indicators in association with reduced severity of caries without improving insulin sensitivity. CONCLUSIONS: Obesity promotes proinflammatory changes within the submandibular gland, without affecting glandular architecture, in association with rampant caries; Cr(Pic)3 treatment provided some protective effects.


Assuntos
Suscetibilidade à Cárie Dentária , Cárie Dentária/etiologia , Obesidade/fisiopatologia , Sialadenite/etiologia , Glândula Submandibular/metabolismo , Animais , Suscetibilidade à Cárie Dentária/efeitos dos fármacos , Suplementos Nutricionais , Mediadores da Inflamação/metabolismo , Resistência à Insulina/fisiologia , Masculino , NF-kappa B/metabolismo , Obesidade/complicações , Ácidos Picolínicos/farmacologia , Ratos , Ratos Zucker
12.
J Craniofac Surg ; 22(2): 762-6, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21415661

RESUMO

Malignant peripheral nerve sheath tumor is a common tumor that rarely affects the head and neck region. The patient presented in this report is a teenage girl presented with a lesion in the right body of the mandible with severe disfigurement of the lower face. The lesion was first histopathologically diagnosed as embryonal rhabdomyosarcoma. After excision, however, the histopathology report proved the diagnosis of malignant peripheral nerve sheath tumor.


Assuntos
Neoplasias Mandibulares/diagnóstico , Neoplasias Mandibulares/terapia , Neoplasias de Bainha Neural/diagnóstico , Neoplasias de Bainha Neural/terapia , Adolescente , Placas Ósseas , Terapia Combinada , Diagnóstico Diferencial , Evolução Fatal , Feminino , Humanos , Procedimentos de Cirurgia Plástica
13.
Ann Plast Surg ; 63(4): 441-8, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19770704

RESUMO

OBJECTIVES: Reconstruction of mandibular segmental bone defects is a challenging task. This study tests a new device used for reconstructing mandibular defects based on the principle of bone transport distraction osteogenesis. METHODS: Thirteen beagle dogs were divided into control and experimental groups. In all animals, a 3-cm defect was created on one side of the mandible. In 8 control animals, the defect was stabilized with a reconstruction plate without further reconstruction and the animals were killed 2 to 3 months after surgery. The remaining 5 animals were reconstructed with a bone transport reconstruction plate, comprising a reconstruction plate with attached intraoral transport unit, and were killed after 1 month of consolidation. RESULTS: Clinical evaluation, cone-beam CT densitometry, three-dimensional histomorphometry, and docking site histology revealed significant new bone formation within the defect in the distracted group. CONCLUSION: The physical dimensions and architectural parameters of the new bone were comparable to the contralateral normal bone. Bone union at the docking site remains a problem.


Assuntos
Placas Ósseas , Regeneração Óssea/fisiologia , Transplante Ósseo/métodos , Traumatismos Mandibulares/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Animais , Densidade Óssea , Modelos Animais de Doenças , Cães , Imageamento Tridimensional , Imuno-Histoquímica , Masculino , Traumatismos Mandibulares/diagnóstico por imagem , Traumatismos Mandibulares/patologia , Probabilidade , Distribuição Aleatória , Estatísticas não Paramétricas , Resistência à Tração , Coleta de Tecidos e Órgãos , Tomografia Computadorizada por Raios X
14.
Artigo em Inglês | MEDLINE | ID: mdl-27746153

RESUMO

OBJECTIVE: The mandible is continuously undergoing remodeling as a result of mechanobiologic factors, such as chewing forces, tooth loss, orthodontic forces, and periodontitis. The effects of mechanical stress and biologic signals in bone homeostasis have been the focus of many investigations. However, much of this research utilized osteocytes derived from long bones, but little is known about the mandible-derived osteocytes. This study tests a protocol to isolate and grow osteocytes from rat mandible. STUDY DESIGN: Rat mandibles were harvested, sectioned into small pieces, and subjected to a sequence chemical treatment and enzymatic digestion. The treated tissues were cultured for a few weeks while cells emerged. Cells were sorted by using the osteocyte marker podoplanin, an early marker for osteocyte differentiation. The cells were then characterized according to morphology, biochemical markers (osteocalcin, podoplanin, and sclerostin), and alkaline phosphatase activity and compared with an isotype cell line MLO-Y4 cells. RESULTS: The mandibular osteocytic cells had stellate shape and were positive for osteocalcin, podoplanin, and sclerostin and lower alkaline phosphatase activity compared with MLO-Y4 osteocyte-like cells. CONCLUSIONS: The protocol to isolate osteocyte-like cells will allow the investigators to investigate the mechanobiologic differences in biomechanical response between these mandibular and long bone osteocyte-like cells under various conditions.


Assuntos
Mandíbula/citologia , Osteócitos/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Proteínas Morfogenéticas Ósseas/metabolismo , Diferenciação Celular , Linhagem Celular , Células Cultivadas , Marcadores Genéticos , Imuno-Histoquímica , Masculino , Glicoproteínas de Membrana/metabolismo , Microscopia Eletrônica de Transmissão , Osteocalcina/metabolismo , Ratos , Ratos Sprague-Dawley
15.
Artigo em Inglês | MEDLINE | ID: mdl-27039006

RESUMO

OBJECTIVES: The objective of this study was to evaluate the baseline differences between alveolar and basal areas of the rat mandible. STUDY DESIGN: Rat mandibular alveolar and basal bones were evaluated using histology and micro-computed tomography to compare osteocyte number as well as bone density and architecture and polymerase chain reaction to measure gene expression levels. RESULTS: Micro-computed tomography data indicated that basal bone is denser and less porous than alveolar bone. Histologic analysis showed that alveolar bone has more osteocytes per unit area compared with basal bone. Real-time polymerase chain reaction results showed higher levels of expression of the following genes in basal bone than in alveolar bone: SOST, E-11, DMP-1, and MEPE. CONCLUSIONS: Three of these gene products are associated with mature osteocytes, and this suggests that basal bone has more mature osteocyte phenotypes compared with alveolar bone. These findings are suggestive of fewer bone mineralization units and therefore a slower remodeling rate.


Assuntos
Expressão Gênica , Mandíbula/anatomia & histologia , Mandíbula/diagnóstico por imagem , Animais , Densidade Óssea/genética , Proteínas Morfogenéticas Ósseas/genética , Calcificação Fisiológica/genética , Proteínas da Matriz Extracelular/genética , Marcadores Genéticos/genética , Glicoproteínas/genética , Masculino , Glicoproteínas de Membrana/genética , Osteócitos/citologia , Fenótipo , Fosfoproteínas/genética , Reação em Cadeia da Polimerase , Ratos , Ratos Sprague-Dawley , Microtomografia por Raio-X
16.
J Oral Implantol ; 41(2): e24-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24295432

RESUMO

Long-term use of intravenous bisphosphonates, such as zoledronic acid (zoledronate), has been linked to bisphosphonate-related osteonecrosis of the jaw (BRONJ). Invasive dental surgery seems to trigger the bone necrosis in most cases. To determine the effects of zoledronic acid on the vascular structure of the rat mandible. Extracted of the mandibular first molar in rats that received 2 IV injections of zoledronate (20 µg/kg), 4 weeks apart. Zoledronate-treated rats (n = 18) were then compared to a control group of untreated rats (n = 18). At the fourth, eighth, and 12th week after molar extraction, 8 rat mandibles from each group were perfused with 35% radiopaque triphenylbismuth in methyl methacrylate via carotid artery perfusion. Mandibles were harvested and examined by micro-CT to assess the spatial and dimensional changes of the vasculature as a result of zoledronate treatment. The micro-CT analysis showed that zoledronic acid-treated rats had blood vessels that were thicker, less connected, and less ordered than control rats that were not exposed to zoledronic acid. This study demonstrated that treatment with zoledronic acid in rats is associated with vascular changes in alveolar bone. Further studies are underway to explore whether these vascular changes contribute to the pathogenesis of BRONJ.


Assuntos
Conservadores da Densidade Óssea , Difosfonatos , Modelos Animais de Doenças , Imidazóis , Mandíbula , Animais , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Mandíbula/irrigação sanguínea , Ratos , Ratos Sprague-Dawley
17.
PLoS One ; 10(7): e0132520, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26186665

RESUMO

This study aims to develop a reproducible rat model for post-traumatic bisphosphonate-related osteonecrosis of the jaw (BRONJ). In our previous studies using dental extraction as an inducing factor, only 30%-60% of zoledronate-treated animals fulfilled the definition of clinical BRONJ. We modified the zoledronate regimen and introduced repeated surgical extraction to illicit quantifiable BRONJ in all animals. Eighty retired-breeder female Sprague-Dawley rats were divided between the treatment (i.v. zoledronate; 80 µg/kg/week for 13 weeks) and control (saline) groups. On week 13, the left mandibular first molar was surgically extracted, followed by the second molar a week later. Animals were euthanized at 1-week, 2-weeks, and 8-weeks following extraction. The occurrence and severity of BRONJ were scored in each animal based on gross and MicroCT analysis. Parameters of bone formation and osteoclast functions at the extraction site were compared between groups. All zoledronate-treated animals developed a severe case of BRONJ that fulfilled the clinical definition of the condition in humans. Osteoclast attachment continued to be defective eight weeks after stopping the treatment. There were no signs of kidney or liver toxicity. Our data confirmed that repeated surgical extraction (major trauma) by itself consistently precipitated massive bone necrosis in ZA-treated animals, eliminating the need to induce pre-existing infection or comorbidity. These results will be the basis for further studies examining the in-vivo pathogenesis and prevention of BRONJ.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Difosfonatos/efeitos adversos , Imidazóis/efeitos adversos , Ferimentos e Lesões/complicações , Fosfatase Ácida/metabolismo , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico por imagem , Modelos Animais de Doenças , Feminino , Isoenzimas/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Mandíbula/diagnóstico por imagem , Mandíbula/efeitos dos fármacos , Mandíbula/patologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/patologia , Ratos Sprague-Dawley , Fosfatase Ácida Resistente a Tartarato , Extração Dentária , Cicatrização/efeitos dos fármacos , Microtomografia por Raio-X , Ácido Zoledrônico
18.
Stem Cell Res ; 10(1): 36-47, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23089627

RESUMO

Ascorbic acid (Vitamin C) has a critical role in bone formation and osteoblast differentiation, but very little is known about the molecular mechanisms of ascorbic acid entry into bone marrow stromal cells (BMSCs). To address this gap in knowledge, we investigated the identity of the transport system that is responsible for the uptake of ascorbic acid into bone marrow stromal cells (BMSCs). First, we examined the expression of the two known isoforms of the sodium-coupled ascorbic acid transporter, namely SVCT1 and SVCT2, in BMSCs (Lin-ve Sca1+ve) and bone at the mRNA level. Only SVCT2 mRNA was detected in BMSCs and bone. Uptake of ascorbic acid in BMSCs was Na(+)-dependent and saturable. In order to define the role of SVCT2 in BMSC differentiation into osteoblasts, BMSCs were stimulated with osteogenic media for different time intervals, and the activity of SVCT2 was monitored by ascorbic acid uptake. SVCT2 expression was up-regulated during the osteogenic differentiation of BMSCs; the expression was maximal at the earliest phase of differentiation. Subsequently, osteogenesis was inhibited in BMSCs upon knock-down of SVCT2 by lentivirus shRNA. We also found that the expression of the SVCT2 could be negatively or positively modulated by the presence of oxidant (Sin-1) or antioxidant (Ascorbic acid) compounds, respectively, in BMSCs. Furthermore, we found that this transporter is also regulated with age in mouse bone. These data show that SVCT2 plays a vital role in the osteogenic differentiation of BMSCs and that its expression is altered under conditions associated with redox reaction. Our findings could be relevant to bone tissue engineering and bone related diseases such as osteoporosis in which oxidative stress and aging plays important role.


Assuntos
Células-Tronco Mesenquimais/metabolismo , Transportadores de Sódio Acoplados à Vitamina C/metabolismo , Animais , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Osso e Ossos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos C57BL , Osteogênese/efeitos dos fármacos , Oxirredução , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Crânio/metabolismo , Sódio/metabolismo , Transportadores de Sódio Acoplados à Vitamina C/antagonistas & inibidores , Transportadores de Sódio Acoplados à Vitamina C/genética , Fatores de Tempo , Engenharia Tecidual , Regulação para Cima/efeitos dos fármacos
19.
Int J Oral Maxillofac Implants ; 28(3): 677-86, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23748297

RESUMO

PURPOSE: The purpose of this study was to compare the osseointegration of dental implants placed in canine mandibular bone and in regenerated bone produced by bone transport distraction osteogenesis. MATERIALS AND METHODS: Ten adult foxhounds were divided into two groups of five animals each. In all animals, a 40-mm defect was created on one side of the mandible. A bone transport reconstruction plate was used to stabilize the mandible and regenerate bone. Six weeks after the distraction period was finished, dental implants were placed in regenerated and native mandibular bone. The animals were sacrificed after another 6 and 12 weeks of healing, respectively. RESULTS: Microcomputed tomographic evaluation showed that bone volume fraction (BV/TV) was greater at the coronal regions of the implants and decreased toward the apical regions. There was an increase in BV/TV around implants placed in regenerated bone from 6 to 12 weeks of healing. The regenerated group showed lower BV/TV at 6 weeks versus implants placed in native bone but had reached the same levels as the native bone at 12 weeks. Histology showed that direct bone-to-implant contact was greater for implants placed in native bone than for those placed in regenerated bone for both time periods. The removal torque of the implants placed in native bone was higher at 6 weeks than that of implants placed in regenerated bone. At 12 weeks, there were no statistically significant differences in removal torque between the groups. CONCLUSIONS: Bone was successfully regenerated in all animals. The implants placed entirely in regenerated bone were osseointegrated. The regenerated bone around the implants became denser over time. This finding suggests that implants placed entirely in regenerated bone will be as well integrated as implants in native mandibular bone by 12 weeks after placement.


Assuntos
Implantação Dentária Endóssea , Mandíbula/cirurgia , Osseointegração/fisiologia , Osteogênese por Distração/métodos , Animais , Regeneração Óssea/fisiologia , Implantação Dentária Endóssea/métodos , Implantes Dentários , Cães , Mandíbula/diagnóstico por imagem , Mandíbula/patologia , Cicatrização , Microtomografia por Raio-X
20.
Oral Surg Oral Med Oral Pathol Oral Radiol ; 114(5 Suppl): S179-89, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23063396

RESUMO

This literature review was performed to illustrate and compare different alveolar ridge augmentation procedures before dental implant placement. The review was based on clinical and research studies listed in Pubmed. There is not enough evidence to support any single method as gold standard for any given condition, and choice seemed to be based on personal preferences. There is a lack of long-term survival data or success rates of grafting materials regarding donor and recipient sites. Although ridge splitting and distraction osteogenesis techniques eliminate donor site morbidity, circumvent the use of grafting materials, and reduce the operation time, some disadvantages and limitations should be considered. More studies are needed to compare the fate and characteristics of new bone obtained by these different procedures, as well as subsequent implant survival rates.


Assuntos
Perda do Osso Alveolar/cirurgia , Processo Alveolar/cirurgia , Aumento do Rebordo Alveolar/métodos , Implantação Dentária Endóssea/métodos , Perda do Osso Alveolar/classificação , Processo Alveolar/diagnóstico por imagem , Humanos , Radiografia
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