Oral squamous carcinoma cells secrete RANKL directly supporting osteolytic bone loss

Objective: Local invasion of bone is a frequent complication of oral squamous cell carcinoma (OSCC). Development of these osteolytic lesions is mediated by osteoclasts. Receptor activation of NF-kappa B ligand (RANKL) signaling, counteracted by osteoprotegerin (OPG), regulates osteoclastogenesis. Previous studies in rodent models have demonstrated that inhibition of RANKL decreases tumor growth and lesions within bone. However, the contributory role of OSCC cells to this disease process has yet to be defined.Methods: RANKL expression was assessed in a panel of OSCC cell lines by qPCR, flow cytometry, and ELISA. Induction of osteoclastogenesis was assessed by co-culture with macrophages or with OSCC-derived conditioned medium. In an animal model of bone invasion, nude mice were injected intratibially with UMSCC-11B cells expressing a RANKL luciferase promoter to detect tumor-derived RANKL activity. Osteolytic lesions were analyzed by X-ray, micro-CT, and histological methods. RANKL expression was assessed in human OSCC tissues by immunohistochemistry.Results: We demonstrated that OSCCs express varied levels of all RANKL isoforms, both membrane-bound and soluble RANKL. Both co-culture and treatment with OSCC-conditioned media induced osteoclastogenesis. In mice, we demonstrated human RANKL promoter activity during bone invasion. Over the course of the experiment, animals suffered osteolytic lesions as RANKL-driven luciferase expression increased with time. After 8 weeks, human-derived RANKL was detected in areas of bone resorption by immunohistochemistry. Similar epithelial RANKL expression was detected in human OSCC tissues.Conclusion: These data demonstrate the ability of OSCCs to produce RANKL, directly altering the tumor microenvironment to increase osteoclastogenesis and mediate local bone invasion. (C) 2012 Elsevier Ltd. All rights reserved.

Peripheral Blood Mononuclear Phagocytes From Patients With Chronic Periodontitis Are Primed for Osteoclast Formation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Severe secondary hyperparathyroidism and panoramic radiography parameters

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Total Spontaneous Regression of a Central Giant Cell Granuloma After Incisional Biopsy: A Four-Year Follow-Up Case Report

Central giant cell granuloma (CGCG) of the jaws represents a localized and benign neoplastic lesion sometimes characterized by aggressive osteolytic proliferation. The World Health Organization defines it as an intraosseous lesion composed of cellular and dense connective tissues that contain multiple hemorrhagic foci, an aggregation of multinucleated giant cells, and occasional bone tissue trabeculae. The origin of this lesion is uncertain; however, factors such as local trauma, inflammation, intraosseous hemorrhage, and genetic abnormalities have been identified as possible causes. CGCG generally affects those younger than 30 years and occurs more frequently in women (2: 1). This lesion corresponds to approximately 7% of all benign tumors of the jaws, with prevalence in the anterior region of the jaw. Aggressive lesions are characterized by symptoms, such as pain, numbness, rapid growth, cortical perforation, root resorption, and a high recurrence rate after curettage. In contrast, nonaggressive CGCGs have a slow rate of growth, may contain sparse trabeculation, and are less likely to move teeth or cause root resorption or cortical perforation. Nonaggressive CGCGs are generally asymptomatic lesions and thus are frequently found on routine dental radiographs. Radiographically, the 2 forms of CGCG present as radiolucent, expansive, unilocular or multilocular masses with well-defined margins. The histopathology of CGCG is characterized by multinucleated giant cells, surrounded by round, oval, and spindle-shaped mononuclear cells, scattered in dense connective tissue with hemorrhagic and abundant vascularization foci. The final diagnosis is determined by histopathologic analysis of the biopsy specimen. The preferred treatment for CGCG consists of excisional biopsy, curettage with a safety margin, and partial or total resection of the affected bone. Conservative treatments include local injections of steroids, calcitonin, and antiangiogenic therapy. Drug treatment using antibiotics, painkillers, and corticosteroids and clinical and radiographic monitoring are necessary for approximately 10 days after surgery. There are only a few cases of spontaneous CGCG regression described in the literature; therefore, a detailed case report of CGCG regression in a 12-yearold boy with a 4-year follow-up is presented and compared with previous studies. (c) 2014 American Association of Oral and Maxillofacial Surgeons

Estudo comparativo da reparação de membranas sinusais e da formação óssea no interior do seio maxilar em coelhos após enxertos ósseos (Sinus Lift), com selante de fibrina e membrana de colageno

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeito de um curcumin modificado quimicamente sobre a reabsorção óssea inflamatória e apoptose: estudos in vivo e in vitro

Pós-graduação em Odontologia - FOAR

Efeito do extrato insaponificável de abacate e soja na doença periodontal induzida, na osseointegração de implantes e no reparo de defeitos críticos de calvaria de ratos

Pós-graduação em Odontologia - FOAR

Estudo comparativo do processo de reparo utilizando osso autógeno e beta-tricálcio fosfato em levantamento do assoalho do seio maxilar em humanos: análise tomográfica, histológica, histométrica e imunoistoquímica

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

MTA e hidróxido de cálcio como materiais obturadores de canal radicular em reimplante tardio de dente de macaco

O tratamento endodôntico é uma etapa importante do protocolo de atendimento do reimplante dentário e tem uma relação direta com o aparecimento das reabsorções radiculares, maior causa de perda dos dentes reimplantados. O objetivo do trabalho foi analisar o processo de reparo no reimplante tardio de dente de macaco, utilizando o hidróxido de cálcio (Ca(OH)2) e o MTA como materiais obturadores de canal. Cinco macacos Cebus apella adultos tiveram seus incisivos laterais superiores e inferiores, direito e esquerdo, extraídos e deixados em meio ambiente por 60 minutos. Decorrido esse período, foi realizado o preparo biomecânico dos canais e os dentes foram divididos em dois grupos experimentais: grupo I - canal preenchido com pasta de Ca(OH)2 e grupo II - canal preenchido com MTA (Angelus®). Após o selamento da abertura coronária com ionômero de vidro, o ligamento periodontal foi removido e os dentes imersos em solução de fluoreto de sódio 2%, pH 5,5, por 10 minutos. Em seguida, os alvéolos foram irrigados com soro fisiológico e os dentes reimplantados e contidos por 30 dias com fio de aço e resina composta. A eutanásia dos animais foi realizada 60 dias após o reimplante. Os espécimes de ambos os grupos apresentaram reabsorção por substituição e pontos de anquilose ao longo dos três terços radiculares e ausência de reabsorção inflamatória. Não houve diferença significante entre os dois grupos com relação à reabsorção por substituição, porém a quantidade de anquilose foi significativamente maior no grupo do Ca(OH)2. Baseado nesses resultados conclui-se que o MTA pode ser uma opção clínica viável para a obturação de dentes tardiamente reimplantados que necessitam de um longo período de curativo com hidróxido de cálcio.

Apical periodontitis and periodontal disease increase serum IL-17 levels in normoglycemic and diabetic rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Spontaneous osteonecrosis of the jaws in the maxilla of mice on antiresorptive treatment: A novel ONJ mouse model

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

3D osteoarthritic changes in TMJ condylar morphology correlates with specific systemic and local biomarkers of disease

Objective: To assess 3D morphological variations and local and systemic biomarker profiles in subjects with a diagnosis of temporomandibular joint osteoarthritis (TMJ OA).Design: Twenty-eight patients with long-term TMJ OA (39.9 +/- 16 years), 12 patients at initial diagnosis of OA (47.4 +/- 16.1 years), and 12 healthy controls (41.8 +/- 12.2 years) were recruited. All patients were female and had cone beam CT scans taken. TMJ arthrocentesis and venipuncture were performed on 12 OA and 12 age-matched healthy controls. Serum and synovial fluid levels of 50 biomarkers of arthritic inflammation were quantified by protein microarrays. Shape Analysis MANCOVA tested statistical correlations between biomarker levels and variations in condylar morphology.Results: Compared with healthy controls, the OA average condyle was significantly smaller in all dimensions except its anterior surface, with areas indicative of bone resorption along the articular surface, particularly in the lateral pole. Synovial fluid levels of ANG, GDF15, TIMP-1, CXCL16, MMP-3 and MMP-7 were significantly correlated with bone apposition of the condylar anterior surface. Serum levels of ENA-78, MMP-3, PAI-1, VE-Cadherin, VEGF, GM-CSF, TGF beta b1, IFN gamma g, TNF alpha a, IL-1 alpha a, and IL-6 were significantly correlated with flattening of the lateral pole. Expression levels of ANG were significantly correlated with the articular morphology in healthy controls.Conclusions: Bone resorption at the articular surface, particularly at the lateral pole was statistically significant at initial diagnosis of TMJ OA. Synovial fluid levels of ANG, GDF15, TIMP-1, CXCL16, MMP-3 and MMP-7 were correlated with bone apposition. Serum levels of ENA-78, MMP-3, PAI-1, VE-Cadherin, VEGF, GM-CSF, TGF beta 1, IFN gamma, TNF alpha, IL-1 alpha, and IL-6 were correlated with bone resorption. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.

The edentulous ridge expansion (ERE) technique an experimental study in the dog

Objective: To compare the healing and bony crest resorption at implants installed conventionally or applying an edentulous ridge expansion (ERE) technique in the maxilla.Material and methods: In six Labrador dogs, the first and second maxillary incisors were extracted bilaterally. In the left side of the maxilla (Test), the flaps were elevated and the buccal plate of the alveoli and septa was removed. After 3 months of healing, partial-thickness (split) flaps were dissected and the residual alveolar bone was exposed. In the right side of the maxilla, an implant was installed conventionally (Type IV; Control) while, in the left side, the ERE technique was adopted. Hence, an expansion of the buccal bony crest was obtained, and the implant was subsequently installed (Test). After 3 months of healing, biopsies were obtained and ground sections were prepared for histological analyses.Results: A buccal vertical resorption of the bony crest of 2.2 +/- 1.2 mm and 1.6 +/- 0.7 mm was found at the test and control sites, respectively. The difference, however, did not reach statistical significance. The coronal level of osseointegration at the buccal aspect was located at 3.1 +/- 1.0 mm and 2.2 +/- 0.7 mm from the implant shoulder at the test and control sites, respectively, the difference being statistically significant. The mean values of the mineralized bone-to-implant contact (MBIC%) ranged from 43% to 48% at the buccal and lingual sites. No differences reached statistical significance.Conclusions: Implants installed by applying an ERE technique may osseointegrate similarly to conventional implant installation. However, vertical and horizontal resorption of the displaced buccal bony wall occurred as well.

Influence of immediate loading on healing of implants installed with different insertion torques - an experimental study in dogs

Objective: To evaluate the influence of different insertion torques on healing of implants loaded immediately or left unloaded.Material and methods: In six Labrador dogs, all mandibular premolars and molars were extracted. After 4 months of healing, flaps were elevated, and two implant sites were prepared at each side of the mandible. The distal sites were prepared conventionally while the mesial sites were underprepared by 0.3 mm. As a consequence, different final insertion torques of about 30 Ncm at the distal and >70 Ncm at the mesial sites were recorded. Healing abutments were applied to the left and transmucosal abutments to the right side. Flaps were sutured, crown preparation of the upper right second and third premolars was performed, and impressions were taken. Within 24 h, crowns were cemented both to implants and teeth in the right side of the mouth. After 4 months, the animals were sacrificed and ground sections obtained for histological evaluation.Results: A higher buccal bony crestal resorption and a more apical position of the coronal level of osseointegration were found at the loaded compared with the unloaded sites. MBIC% and percentages of peri-implant mineralized tissue (MB%) were higher at the loaded compared with the unloaded sites. Moreover, a higher MBIC% was found at the lower compared with the higher final insertion torque.Conclusions: Immediate loading does not seem to have a negative effect on osseointegration. High torque values for the immediate loading procedures were not necessary. Probably, low torque values, were sufficient to obtain primary stability and hence may provide better osseointegration than high torque value.

Hard and soft tissue changes around implants installed in regular-sized and reduced alveolar bony ridges. An experimental study in dogs

Objective: To study bony and soft tissue changes at implants installed in alveolar bony ridges of different widths.Material and methods: In 6 Labrador dogs, the mandibular premolars and first molars were extracted, and a buccal defect was created in the left side at the third and fourth premolars by removing the buccal bone and the inter-radicular and interdental septa. Three months after tooth extraction, full-thickness mucoperiosteal flaps were elevated, and implants were installed, two at the reduced (test) and two at the regular-sized ridges (control). Narrow or wide abutments were affixed to the implants. After 3 months, biopsies were harvested, and ground sections prepared for histological evaluation.Results: A higher vertical buccal bony crest resorption was found at the test (1.5 +/- 0.7 mm and 1.0 +/- 0.7 mm) compared to the control implants (1.0 +/- 0.5 mm and 0.7 +/- 0.4 mm), for both wide and narrow abutment sites. A higher horizontal alveolar resorption was identified at the control compared to the test implants. The difference was significant for narrow abutment sites. The peri-implant mucosa was more coronally positioned at the narrow abutment, in the test sites, while for the control sites, the mucosal adaptation was more coronal at the wide abutment sites. These differences, however, did not reach statistical significance.Conclusions: Implants installed in regular-sized alveolar ridges had a higher horizontal, but a lower vertical buccal bony crest resorption compared to implants installed in reduced alveolar ridges. Narrow abutments in reduced ridges as well as wide abutments in regular-sized ridges yielded less soft tissue recession compared to their counterparts.