Loss of KDM4B impairs osteogenic differentiation of OMSCs and promotes oral bone aging / 国际口腔科学杂志·英文版

Aging of craniofacial skeleton significantly impairs the repair and regeneration of trauma-induced bony defects, and complicates dental treatment outcomes. Age-related alveolar bone loss could be attributed to decreased progenitor pool through senescence, imbalance in bone metabolism and bone-fat ratio. Mesenchymal stem cells isolated from oral bones (OMSCs) have distinct lineage propensities and characteristics compared to MSCs from long bones, and are more suited for craniofacial regeneration. However, the effect of epigenetic modifications regulating OMSC differentiation and senescence in aging has not yet been investigated. In this study, we found that the histone demethylase KDM4B plays an essential role in regulating the osteogenesis of OMSCs and oral bone aging. Loss of KDM4B in OMSCs leads to inhibition of osteogenesis. Moreover, KDM4B loss promoted adipogenesis and OMSC senescence which further impairs bone-fat balance in the mandible. Together, our data suggest that KDM4B may underpin the molecular mechanisms of OMSC fate determination and alveolar bone homeostasis in skeletal aging, and present as a promising therapeutic target for addressing craniofacial skeletal defects associated with age-related deteriorations.

Platelet Rich Plasma (PRP) Produces an Atherofibrotic Histophenotype During Craniofacial Bone Repair Due to Changes of Immunohistochemical Expression of Erk1/2, p38α /β, Adiponectin and Elevated Presence of Cells Exhibiting B-scavenger Receptor (CD36+)

Abstract The platelet-extracellular matrix interaction in platelet rich plasma (PRP) through thrombospondin receptor-CD36 induces the secretion of growth factors responsible for cellular proliferation and differentiation during the repair process. Since CD36 also acts as a class B-scavenger-receptor for development of foam-like cells and mitogen-activated kinases, such as Erk1/2 and p38α/β, are important proteins activated by platelet growth factor, the aim of this study was to evaluate the immunohistochemical presence of CD36, Erk1/2, p38α/β during the bone repair treated and non-treated with PRP and to compare these results with the histomorphometry of repair. Simultaneously, the immunopresence of adiponectin was analyzed, which may contribute to osteogenesis at the same time it inhibits fibrosis and impairs adipogenesis and foam cell formation in the medullary area. An artificial bone defect measuring 5×1 mm was produced in the calvaria of 56 Wistar rats. The defects were randomly treated with autograft, autograft+PRP, PRP alone and sham. The animals were euthanized at 2 and 6 weeks post-surgery. Data were analyzed by ANOVA followed by non-parametric test Student Newman-Keuls (p<0.05) for histomorphometric and immunohistochemical interpretation. The results revealed that in specimens that received PRP the immunopositivity for Erk1/2, p38α/β and CD36 proteins increased significantly while the immunohistochemical expression of adiponectin decreased simultaneously. There was also an accentuated reduction of bone matrix deposition and increase of the medullary area represented by fibrosis and/or presence of foam-like cells, which exhibited immunophenotype CD36+adiponectin. The findings of this study suggest that PRP acted as an inhibitor of osteogenesis during the craniofacial bone repair and induced a pathological condition that mimics an atherofibrotic condition.

Resumo A interação da matriz extracelular-plaquetas no plasma rico em plaquetas (PRP) através de receptor trombospondina CD36 induz a secreção de fatores de crescimento responsáveis pela proliferação e diferenciação celular durante o processo de reparo. Uma vez que o CD36 também age como receptor scavenger de classe B para o desenvolvimento de células do tipo espuma, e as quinases ativadas por mitógenos, tais como ERK1/2 e p38α/β, são importantes proteínas ativadas por fator de crescimento das plaquetas, o objetivo deste estudo foi avaliar a presença imunoistoquímica de CD36, ERK1/2, p38α/β durante o reparo ósseo tratado e não-tratado com PRP e comparar estes resultados com a histomorfometria do reparo. Simultaneamente, analisou-se a imunopresença da adiponectina, que pode contribuir para osteogênese ao mesmo tempo que inibe a fibrose e prejudica a formação de células tipo espuma/xantomatosas na área medular. Um defeito artificial de osso medindo 5×1 mm foi produzido na calvária de 56 ratos Wistar. Os defeitos foram tratados aleatoriamente com auto-enxerto, enxerto autógeno+PRP, PRP apenas e sham. Os animais foram sacrificados 2 e 6 semanas pós-cirurgia. Os dados foram examinados por meio de ANOVA, seguido pelo teste não-paramétrico Student Newman-Keuls (p<0,05) para a interpretação histomorfométrica e imunoistoquímica. Os resultados revelaram que as amostras que receberam PRP aumentaram significativamente a imunopositividade para as proteínas ERK1/2, p38α/β e CD36, simultaneamente à diminuição de expressão imunoistoquímica da adiponectina. Houve também expressiva redução de deposição de matriz óssea e aumento da área medular representada por fibrose e/ou presença de células do tipo espuma que apresentaram imunofenótipo CD36 + adiponectina. Estes resultados sugerem que o PRP atuou como um inibidor da osteogênese durante o reparo ósseo craniofacial e induziu uma condição patológica que mimetiza uma condição aterofibrótica.

Alterações Ósseas e do Sistema Estomatognático associadas a Doenças Endócrino Metabólicas / Cambios en los huesos y del sistema estomatognático asociadas con las enfermedades endocrino-metabólicas / Diseases Bone Changes and changes in the Stomatognathic System Associated with Metabolic Endocrine Diseases

Introdução: a prevalência de doenças endócrino-metabólicas tem aumentado nos últimos anos com a melhoria da expectativa de vida da população. Diabete Melittus, hipotireoidismo, hipertireoidismo, hipoparatireoidismo e hiperparatireoidismo podem levar as alterações no sistema estomatognático, contudo, a literatura ainda é limitada nesta área. Objetivo: Abordar as características e o processo fisiopatológico de doenças endócrino-metabólicas, com destaque para as alterações ósseas e do sistema estomatognático. Metodologia: Os dados foram coletados através da seleção de artigos sobre alterações ósseas e do sistema estomatognático associadas ao hipotireoidismo, hipertireoidismo, hipoparatireoidismo, hiperparatireoidismo e diabete mellitus, publicados nos bancos de dados, Bireme, MEDLINE e Scielo. Resultados: Foram coletados 73 artigos publicados na literatura entre os anos 1995 e 2012, dos quais 40 foram selecionados por se enquadrar no tema proposto. A literatura consultada demonstrou que alterações dos níveis séricos dos hormônios tireoidianos e do paratormônio, assim como diabete mellitus, influenciam no metabolismo ósseo. Atrasos na esfoliação e erupção dentária, no crescimento e desenvolvimento ósseo são observados no hipotireoidismo, enquanto o hipertireoidismo apresenta densidade óssea mineral diminuída, osteoporose dos ossos maxilares, esfoliação acelerada dos dentes decíduos e erupção prematura dos permanentes. No hipoparatireoidismo, observa-se osteoesclerose, dentição hipoplásica e reduzida remodelação óssea. Intensa atividade osteoclástica, ausência de lâmina dura e tumor marrom podem estar presentes no hiperparatireoidismo. Diabete mellitus pode ocasionar oesteoporose, doença periodontal e hipoplasia de esmalte. Embora conhecidas, a magnitude e as causas destas alterações no sistema estomatognático ainda são pouco elucidadas. Conclusões: É imprescindível que o cirurgião dentista tenha conhecimento sobre as manifestações locais ou sistêmicas associadas a estas desordens endócrino-metabólicas que podem acometer os pacientes, para que possa reconhecê-las e contribuir com o seu diagnóstico e tratamento precoces(AU)

Introducción: La prevalencia de las enfermedades endocrino-metabólicas se ha incrementado en los últimos años por el incremento de la esperanza de vida de la población. La diabetes mellitus, hipotiroidismo, hipertiroidismo, hipoparatiroidismo e hiperparatiroidismo pueden presentar alteraciones en el sistema estomatognático, sin embargo, los estudios encontrados en la literatura son todavía limitados en esta área. Objetivo: abordar las características y procesos fisiopatológicos de estas enfermedades y los cambios especialmente en los huesos y del sistema estomatognático. Métodos: los datos fueron recolectados a través de la selección de artículos sobre las alteraciones óseas del sistema estomatognático en pacientes afectados con el hipotiroidismo, el hipertiroidismo, el hipoparatiroidismo, el hiperparatiroidismo y la diabetes mellitus, publicada en las bases de datos, BIREME, SciELO y MEDLINE. Resultados: se recolectaron 73 artículos publicados entre los años 1995 y 2012, de los cuales 40 fueron seleccionados por la relación con el tema de interés para nuestro propósito. La literatura ha demostrado que los cambios en los niveles séricos de la hormona tiroidea y paratiroidea, y la diabetes mellitus afectan el metabolismo óseo. En el hipotiroidismo se observan retrasos en la exfoliación y erupción de los dientes, en el crecimiento y desarrollo óseo. El hipertiroidismo, hay disminución de la densidad mineral ósea, osteoporosis de los huesos de la mandíbula, exfoliación acelerada de los dientes temporales y erupción prematura de los permanentes. En el hipoparatiroidismo, se observan osteosclerosis, dientes hipoplásicos, y remodelación ósea reducida. Puede estar presente intensa actividad de los osteoclastos, ausencia de la lámina dura y tumor pardo en el hiperparatiroidismo. La diabete mellitus puede causar oesteoporosis, enfermedad periodontal e hipoplasia del esmalte. Aunque conocidas, la magnitud y las causas de estos cambios en el sistema estomatognático aún no están claros.Conclusiones: es esencial que el dentista tenga conocimiento de las manifestaciones locales o sistémicas asociadas con estos trastornos endocrinos y metabólicos para que pueda reconocerlos y ayudar en el diagnóstico precoz y el tratamiento(AU)

Introduction: the prevalence of endocrine-metabolic diseases has increased in recent years due to improvement of the life expectancy of the population. Diabetes mellitus, hypothyroidism, hyperthyroidism, hypoparathyroidism and hyperparathyroidism may present alterations in the stomatognathic system; however, some studies found in literature are still limited in this area. Objective: to address the characteristics and pathophysiological process of these diseases, especially bone changes and in the stomatognathic system. Methods: data were collected through the selection of articles about bone alterations of the stomatognathic system associated with hypothyroidism, hyperthyroidism, hypoparathyroidism, hyperparathyroidism, and diabetes, published in databases, BIREME, MEDLINE and SciELO. Results: seventy three articles published between 1995 y 2012 were revised, and 40 were selected on the basis of their association with the topic of interest. It has shown that changes in serum levels of thyroid and parathyroid hormones, and diabetes mellitus have an impact on bone metabolism. Delays in tooth eruption and exfoliation, bone growth and development are observed in hypothyroidism, whereas decreased bone mineral density, jawbones osteoporosis, accelerated exfoliation of deciduous teeth and premature eruption of permanent teeth were observed in hyperthyroidism. In hypoparathyroidism, there were osteosclerosis, hypoplastic teeth, and reduced bone remodeling. Intense osteoclastic activity, brown tumors and the absence of lamina dura in hyperparathyroidism may be observed. Diabetes mellitus can cause osteoporosis, periodontal disease and enamel hypoplasia. Although they are known, the magnitude and causes of these changes in the stomatognathic system are still unclear. Conclusions: it is essential that dentist can recognize the local or systemic manifestations associated with these endocrine and metabolic disorders and help to early diagnosis and treatment(AU)

Incidence of the ossified pterygoalar ligamentin Brazilian human skulls and its clinical implications

The ossified pterygoalar ligament is formed between the lateral lamina of the pterygoid process and theinfratemporal surface of the sphenoid bone or its greater wing and was not connected to the sphenoid spine.The aim of this study was to evaluate the incidence of the ossified pterygoalar ligament in Brazilian humanskulls and analyzing its clinical importance. 183 Brazilian adult (between 30 to 60 years old) dry human skullswere evaluated. Was evaluated the incidence of skulls with complete or partial ossification of the pterygoalarligament, bilaterally and unilaterally and in the presence on the right and left sides. Were found 5 skulls had theossified pterygoalar ligament, resulting in an overall incidence of 2.73%. There was 1 skull in the presence ofthe incomplete ossification of the pterygoalar ligament, unilaterally and on the left side resulting in incidence of0.54%. There were 4 skulls in the presence of the complete ossification of the pterygoalar ligament, unilaterallyand on the right side resulting in incidence of 2.18%. The ossified pterygoalar ligament is a major cause of theentrapment of the lingual nerve or a branch of the mandibular nerve and may cause mandibular neuralgia. Theincidence of the ossified pterygoalar ligament and the pterygoalar foramen is low in the Brazilian population.However, these structures have clinical significance as this ligament establish relationships with the ovaleforamen and difficulty in accessing in this foramen in a therapeutic approach.

Fratura de órbita: classificação e tratamento / Orbital and Zygoma fractures: classification assessment and treatment

Foram avaliados clinicamente, 111 paciente de acordo com os métodos de fixação de fraturas orbitárias. Técnicas de fixação rígida, semi-rígidas e com fio de Kirschnner foram avaliadas. Um tratamento baseado na classificação dessas fraturas foi apresentado. Parâmetros clínicos, como anormalidades na posição do globo ocular (distopia e enoftalmia), projeção do malar e teste de sensibilidade foram avaliados. O presente estudo confirma que podemos usar material de baixo custo com bons resultados.

We evaluated 111 pacientes to assess clinically the results of fixation methods on orbital and zygoma fractures. Rigid plate fixation, wire techniques and fixation with Kirschnner were used. A treatment guidline based on classification of orbital fractures is presented. The major clinical parameters assessed were globe position abnormalities (enophthalmus and dystopia), malar projection and cheek sensation. The present study confirms that we can use low-cost material with good results.