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1.
Sci Rep ; 8(1): 13551, 2018 09 10.
Article in English | MEDLINE | ID: mdl-30202094

ABSTRACT

Runx2 and Sp7 are essential transcription factors for osteoblast differentiation. However, the molecular mechanisms responsible for the proliferation of osteoblast progenitors remain unclear. The early onset of Runx2 expression caused limb defects through the Fgfr1-3 regulation by Runx2. To investigate the physiological role of Runx2 in the regulation of Fgfr1-3, we compared osteoblast progenitors in Sp7-/- and Runx2-/- mice. Osteoblast progenitors accumulated and actively proliferated in calvariae and mandibles of Sp7-/- but not of Runx2-/- mice, and the number of osteoblast progenitors and their proliferation were dependent on the gene dosage of Runx2 in Sp7-/- background. The expression of Fgfr2 and Fgfr3, which were responsible for the proliferation of osteoblast progenitors, was severely reduced in Runx2-/- but not in Sp7-/- calvariae. Runx2 directly regulated Fgfr2 and Fgfr3, increased the proliferation of osteoblast progenitors, and augmented the FGF2-induced proliferation. The proliferation of Sp7-/- osteoblast progenitors was enhanced and strongly augmented by FGF2, and Runx2 knockdown reduced the FGF2-induced proliferation. Fgfr inhibitor AZD4547 abrogated all of the enhanced proliferation. These results indicate that Runx2 is required for the proliferation of osteoblast progenitors and induces proliferation, at least partly, by regulating Fgfr2 and Fgfr3 expression.


Subject(s)
Cell Proliferation/genetics , Core Binding Factor Alpha 1 Subunit/metabolism , Receptor, Fibroblast Growth Factor, Type 2/genetics , Receptor, Fibroblast Growth Factor, Type 3/genetics , Stem Cells/physiology , Animals , Benzamides/pharmacology , Cell Differentiation/genetics , Cell Proliferation/drug effects , Cells, Cultured , Core Binding Factor Alpha 1 Subunit/genetics , Gene Expression Regulation, Developmental , Mice , Mice, Inbred C57BL , Mice, Knockout , Models, Animal , Osteoblasts/physiology , Osteogenesis/genetics , Piperazines/pharmacology , Primary Cell Culture , Pyrazoles/pharmacology , Receptor, Fibroblast Growth Factor, Type 2/antagonists & inhibitors , Receptor, Fibroblast Growth Factor, Type 2/metabolism , Receptor, Fibroblast Growth Factor, Type 3/antagonists & inhibitors , Receptor, Fibroblast Growth Factor, Type 3/metabolism , Sp7 Transcription Factor/genetics
2.
Periodontia ; 19(1): 14-21, 2009. ilus
Article in Portuguese | LILACS, BBO - Dentistry | ID: lil-544295

ABSTRACT

A compreensão dos mecanismos imunológicos da patogênese da doença periodontal tem se tornado cada vez mais importante à medida que as evidências científicas indicam novas possibilidades de tratamento da doença. O, ligante do receptor ativador do fator nuclear KB (RANKL) e a osteoprotegerina (OPG) são moléculas relacionadas à reabsorção óssea na periodontite e podem ser moduladas a partir do uso de drogas. Os inibidores de metaloproteinases da matriz (MMPs), drogas antiinflamatórias e os bisfosfonatos têm demonstrado resultados promissores como terapia adjunta nos casos de periodontite crônica. Sendo assim, o objetivo dessa revisão de literatura é esclarecer os principais componentes e eventos biológicos da resposta imunológica enfatizando o mecanismo de reabsorção óssea na doença periodontal e os potenciais alvos para ação de moduladores da resposta do hospedeiro.


Subject(s)
Bone Resorption , Periodontal Diseases
3.
Braz Dent J ; 19(1): 3-8, 2008.
Article in English | MEDLINE | ID: mdl-19031648

ABSTRACT

Advances in diagnostic research are moving towards methods whereby the periodontal risk can be identified and quantified by objective measures using biomarkers. Patients with periodontitis may have elevated circulating levels of specific inflammatory markers that can be correlated to the severity of the disease. The purpose of this study was to evaluate whether differences in the serum levels of inflammatory biomarkers are differentially expressed in healthy and periodontitis patients. Twenty-five patients (8 healthy patients and 17 chronic periodontitis patients) were enrolled in the study. A 15 mL blood sample was used for identification of the inflammatory markers, with a human inflammatory flow cytometry multiplex assay. Among 24 assessed cytokines, only 3 (RANTES, MIG and Eotaxin) were statistically different between groups (p<0.05). In conclusion, some of the selected markers of inflammation are differentially expressed in healthy and periodontitis patients. Cytokine profile analysis may be further explored to distinguish the periodontitis patients from the ones free of disease and also to be used as a measure of risk. The present data, however, are limited and larger sample size studies are required to validate the findings of the specific biomarkers.


Subject(s)
Chronic Periodontitis/blood , Inflammation Mediators/blood , Biomarkers/blood , Chemokine CCL2/blood , Chemokine CCL3/blood , Chemokine CCL4/blood , Chemokine CCL5/blood , Chemokine CXCL9/blood , Chemokines, CC/blood , Cytokines/blood , Fas Ligand Protein/blood , Fibroblast Growth Factor 2/blood , Gingival Hemorrhage/blood , Granulocyte Colony-Stimulating Factor/blood , Granulocyte-Macrophage Colony-Stimulating Factor/blood , Humans , Interferon-gamma/blood , Interleukin-9/blood , Interleukins/blood , Lymphotoxin-alpha/blood , Periodontal Attachment Loss/blood , Periodontal Pocket/blood , Transforming Growth Factor beta/blood
4.
Braz. dent. j ; 19(1): 3-8, 2008. tab
Article in English | LILACS | ID: lil-481120

ABSTRACT

Advances in diagnostic research are moving towards methods whereby the periodontal risk can be identified and quantified by objective measures using biomarkers. Patients with periodontitis may have elevated circulating levels of specific inflammatory markers that can be correlated to the severity of the disease. The purpose of this study was to evaluate whether differences in the serum levels of inflammatory biomarkers are differentially expressed in healthy and periodontitis patients. Twenty-five patients (8 healthy patients and 17 chronic periodontitis patients) were enrolled in the study. A 15 mL blood sample was used for identification of the inflammatory markers, with a human inflammatory flow cytometry multiplex assay. Among 24 assessed cytokines, only 3 (RANTES, MIG and Eotaxin) were statistically different between groups (p<0.05). In conclusion, some of the selected markers of inflammation are differentially expressed in healthy and periodontitis patients. Cytokine profile analysis may be further explored to distinguish the periodontitis patients from the ones free of disease and also to be used as a measure of risk. The present data, however, are limited and larger sample size studies are required to validate the findings of the specific biomarkers.


Avanços no diagnóstico da doença periodontal levam a métodos nos quais o risco e atividade da doença periodontal podem ser identificados e quantificados por biomarcadores. Pacientes com periodontite podem apresentar elevados níveis circulatórios de marcadores inflamatórios específicos que podem ser correlacionados com a severidade da doença. Portanto, o objetivo desse estudo foi avaliar as diferenças nos níveis séricos de biomarcadores inflamatórios em pacientes saudáveis e com doença periodontal. Foram incluídos no estudo 25 pacientes (8 saudáveis e 17 com periodontite crônica). Uma amostra de 15 mL de sangue foi obtida para identificar os marcadores inflamatórios simultaneamente utilizando Array de proteínas através de citometria de fluxo. De 24 citocinas inflamatórias analisadas, apenas 3 (RANTES, MIG e Eotaxina) apresentaram diferenças estatisticamente significantes (p<0,05) entre os dois grupos. Conclui-se que alguns marcadores inflamatórios selecionados apresentam diferença de concentração em pacientes com periodontite e saudáveis. A análise do perfil de citocinas pode ser utilizada tanto para distinguir pacientes periodontais de pacientes saudáveis, como para medir o risco à doença. Contudo, mais estudos com número maior de amostras são necessários para validar os achados sobre os biomarcadores específicos.


Subject(s)
Humans , Chronic Periodontitis/blood , Inflammation Mediators/blood , Biomarkers/blood , /blood , /blood , /blood , /blood , Chemokine CXCL9/blood , Chemokines, CC/blood , Cytokines/blood , Fas Ligand Protein/blood , /blood , Gingival Hemorrhage/blood , Granulocyte Colony-Stimulating Factor/blood , Granulocyte-Macrophage Colony-Stimulating Factor/blood , Interferon-gamma/blood , Interleukin-9/blood , Interleukins/blood , Lymphotoxin-alpha/blood , Periodontal Attachment Loss/blood , Periodontal Pocket/blood , Transforming Growth Factor beta/blood
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