ROLE OF OSTEOCLAST PRECURSORS IN PERIODONTAL BONE LOSS
破骨细胞前体在牙周骨丢失中的作用
基本信息
- 批准号:10201568
- 负责人:
- 金额:$ 35.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-07-17 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AgingAlveolar Bone LossBindingBone MarrowBone ResorptionCD4 Positive T LymphocytesCSF1R geneCell Cycle ArrestCell physiologyCellsCharacteristicsChronicDevelopmentDiseaseDown-RegulationExposure toFrequenciesGrantHematopoieticImmune responseImmunosuppressionIn VitroInfectionInflammationInflammatoryInterleukin-1KnowledgeLigandsMacrophage Colony-Stimulating Factor ReceptorMaintenanceMediatingModelingMolecularMusNatureOsteoclastsPathogenesisPathogenicityPathologicPeriodontal DiseasesPeriodontal InfectionPeriodontitisPhenotypePlayPorphyromonas gingivalisPredispositionPreventionProcessPublishingReceptor CellReceptor SignalingRegulationResearchResearch PersonnelRoleSiteSpleenT cell responseT-Cell ProliferationTLR2 geneTNF geneTestingTherapeutic InterventionTimeToll-like receptorsVirulence FactorsWorkalveolar bonebasebonebone losscytokinegranulocyteimmunoregulationin vivoinflammatory bone lossinsightmacrophagemonocytemouse modelnovelnovel diagnosticsnovel therapeutic interventionpathogenpathogenic bacteriaperiodontopathogenprecursor cellpredictive modelingreceptortargeted treatment
项目摘要
Project Summary
Excessive activity of osteoclasts (OC), the body's sole bone resorbing cells, is a major characteristic of
pathogenic bone loss in periodontitis. Although a great deal is known about the process of OC differentiation,
the identity of OC precursors (OCP) in vivo, and their role in periodontitis remain scarce, especially in aging
where the extent of bone loss is increased. Recent studies have identified a cell cycle-arrested quiescent OCP
present in very low numbers. These cells are receptor activator of NF-κB (RANK)-positive and express colony-
stimulating factor-1 receptor (c-fms) at various levels, but scarcely express monocyte/macrophage/ granulocyte
markers. Using in vivo mouse models, we have shown that infection with the periodontal-associated pathogen
Porphyromonas gingivalis (Pg) induces the expansion of an earlier stage c-fms+RANK- OCP (eOCP) and the
more advanced stage RANK+ OCP (rOCP) in bone marrow and spleen. In addition, eOCP and rOCP potently
suppress CD4+ T cell proliferation in vitro, highlighting an important role of OCP in immune regulation.
Moreover, compared to young mice, old mice show increased periodontal bone loss, as well as increased OCP
frequency and osteoclastogenic potential, suggesting that increased OCP pool underlies host susceptibility to
periodontal bone loss in aging. Based on our preliminary studies and published work, we hypothesize that Pg
infection results in the expansion of OCP that can be shunted toward OC formation and bone loss at the
infection/inflammation sites, while at the same time dampen host immune responses, which is beneficial for the
persistence of infection and maintenance of chronic inflammation. We will test our hypothesis by pursuing two
specific aims: 1) Delineate the regulation of OCP following Pg infection; 2) Determine the effect of OCP on host
immune responses and bone loss in vivo to Pg infection. Our proposed studies will provide novel and
significant insight into the pathogenesis of Pg infection and periodontitis leading to the potential development of
targeted therapeutics for inflammatory bone loss diseases.
项目摘要
破骨细胞(OC)是人体唯一的骨吸收细胞,其过度活动是骨吸收障碍的主要特征。
牙周炎中的致病性骨丢失。尽管我们对OC分化的过程了解很多,
OC前体(OCP)在体内的特性及其在牙周炎中的作用仍然很少,特别是在老化中
其中骨丢失的程度增加。最近的研究已经确定了一种细胞周期停滞的静止OCP
以非常低的数量存在。这些细胞是NF-κB受体激活因子(RANK)阳性细胞,表达集落-
刺激因子-1受体(c-fms)在单核细胞/巨噬细胞/粒细胞中有不同水平表达,但几乎不表达
标记。使用体内小鼠模型,我们已经表明,牙周相关病原体的感染
牙龈卟啉单胞菌(Pg)诱导早期c-fms+RANK- OCP(eOCP)扩增,
骨髓和脾脏中更晚期的RANK+ OCP(rOCP)。此外,eOCP和rOCP有效地
在体外抑制CD 4 + T细胞增殖,突出了OCP在免疫调节中的重要作用。
此外,与年轻小鼠相比,老年小鼠显示牙周骨丢失增加,以及OCP增加
频率和破骨细胞生成潜力,表明OCP库增加是宿主对
牙周骨丢失的年龄。基于我们的初步研究和已发表的工作,我们假设Pg
感染导致OCP的扩张,OCP可以转向OC形成和骨丢失,
感染/炎症部位,而同时抑制宿主免疫反应,这对感染/炎症部位是有益的。
感染的持续和慢性炎症的维持。我们将通过追踪两个
具体目的:1)阐明OCP在Pg感染后的调节作用; 2)确定OCP对宿主的影响
免疫反应和骨丢失的体内Pg感染。我们提出的研究将提供新的和
对Pg感染和牙周炎的发病机制有重要的了解,
炎症性骨丢失疾病的靶向治疗。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Ping Zhang其他文献
毛细管电泳差分非接触电导检测器测定氨基酸
- DOI:
- 发表时间:
2012 - 期刊:
- 影响因子:6.1
- 作者:
Yaolong Li;Zhenli Zhang;Ping Zhang;Qi Kang - 通讯作者:
Qi Kang
Ping Zhang的其他文献
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{{ truncateString('Ping Zhang', 18)}}的其他基金
IMPORTANCE OF PERIODONTITIS IN THE INNATE IMMUNE REGULATION OF ALZHEIMER'S DISEASE
牙周炎在阿尔茨海默病先天免疫调节中的重要性
- 批准号:
10658447 - 财政年份:2023
- 资助金额:
$ 35.27万 - 项目类别:
ROLE OF OSTEOCLAST PRECURSORS IN PERIODONTAL BONE LOSS
破骨细胞前体在牙周骨丢失中的作用
- 批准号:
9381236 - 财政年份:2017
- 资助金额:
$ 35.27万 - 项目类别:
Molecular mechanisms of the innate regulation of osteoclastogenesis.
破骨细胞生成先天调节的分子机制。
- 批准号:
8488432 - 财政年份:2012
- 资助金额:
$ 35.27万 - 项目类别:
Molecular mechanisms of the innate regulation of osteoclastogenesis.
破骨细胞生成先天调节的分子机制。
- 批准号:
8383398 - 财政年份:2012
- 资助金额:
$ 35.27万 - 项目类别:
Structual and function of kinase signaling complexes
激酶信号复合物的结构和功能
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10262432 - 财政年份:
- 资助金额:
$ 35.27万 - 项目类别:
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