Controlling chondrocyte matrix degradation and repair in 3-D culture.
控制 3D 培养中的软骨细胞基质降解和修复。
基本信息
- 批准号:8213730
- 负责人:
- 金额:$ 5.22万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-02-01 至 2013-01-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAdherent CultureAdultAffectAlginatesAmericanApoptosisArthritisBiocompatibleCartilageCartilage injuryCattleCellsChemicalsChondrocytesCollagenDataDefectDegenerative polyarthritisDepositionDevelopmentDimensionsDiseaseDoseElementsEmbryoEngineeringEnvironmental Risk FactorEventExtracellular MatrixGene TargetingGenerationsGenesGeneticGenetic DeterminismGenetic ProgrammingGlycosaminoglycansGoalsGrowthHarvestHypertrophyImageIn VitroInflammatoryInjuryKnock-outKnockout MiceKnowledgeLaboratoriesMAP Kinase GeneMAP2K6 geneMAPK14 geneMAPK8 geneMAPK9 geneMEKsMechanicsMentorsMethodsMicroscopyMissionModelingMusMutationNF-kappa BNFKB Signaling PathwayNational Institute of Arthritis and Musculoskeletal and Skin DiseasesOperative Surgical ProceduresPathway interactionsPeptide HydrolasesPharmacologic SubstancePhenotypePopulationProceduresProcessProductionPropertyProteoglycanRelative (related person)ResearchSignal PathwaySignal TransductionSolutionsStressStructureSystemTNF geneTechniquesThinkingTimeTissue EngineeringTissuesTrainingTransgenic OrganismsTraumaTumor Necrosis Factor-alphaUnited States National Institutes of HealthWeight-Bearing stateaggrecanarticular cartilagebasecareercartilage developmentcartilage repaircrosslinkexperiencegene therapyhuman TNF proteinin vitro Modelknockout genemathematical modelmultidisciplinarynovelosteochondral repairosteochondral tissueprogramsrepairedresponsescaffoldsecond harmonicskillstooltwo-photon
项目摘要
DESCRIPTION (provided by applicant): This proposal's long-term objectives are: 1) to provide basic knowledge about how manipulation of Inflammatory signaling pathways can affect the mechanical properties of chondrocyte created neo-matrix, and 2) to create a tissue-engineered surgical solution to restore osteochondral defects. These objectives will be through two specific aims: construction and analysis of tissue-engineered cartilage using 1) genetically-modified mouse chondrocytes with knockout of MKK/MEK3; and 2) pharmacologic inhibition of key signaling pathways (p38 and JNK MARK) that regulate proteoglycan and collagen deposition by chondrocytes in tissue-engineered cartilage. Analysis will encompass mechanical characterization, collagen, crosslink, and GAG content, multiphoton microscopy, and mathematical modeling of the tissue. The goals of this proposal are relevant to the mission of the NIH and NIAMS. Functional engineered cartilage would greatly alleviate cartilage damage which affects ~10% of the population (1). Information gained about the genetic determinants of cartilage neo-matrix formation would increase understanding of cartilage degradation in rheumatoid and osteoarthritis. This proposal has tissue engineering, multiphoton imaging, and mathematical modeling components, and is a multidisciplinary effort to advance basic knowledge of chondrocyte genetic programming in disease and repair processes. Chondrocytes from mice with knockouts and mutations of TNF-alpha and IL-1beta signaling elements will be harvested and seeded within alginate scaffolds to allow neo-matrix development. Tissue mechanical properties, collagen, proteoglycan, and crosslink content will be assessed during culture under normal and transgenic phenotype, and with or without pharmacologic inhibition of the same signaling pathways, known to affect extracellular matrix production (2). Multiphoton imaging will be used to assess collagen deposition and network structure (using signal from second harmonic generation) and collagen crosslink formation (through two-photon autofluorescence signal). Data from the tissue-engineered cartilage will be fit to a cartilage growth mixture model, previously developed to assess native cartilage (3). Every year, cartilage Injury affects nearly 1 million Americans resulting in 200,000 procedures. Injury often leads cryptically to osteoarthritis (1). Tissue-engineered cartilage is a promising method to examine chondrocyte-controlled cartilage degradation and repair. Understanding these processes in vitro would help clinicians control and repair cartilage through pharmaceutical, genetic, and surgical manipulations.
描述(由申请人提供):这项建议的长期目标是:1)提供有关炎症信号通路的操纵如何影响软骨细胞产生的新基质的机械性能的基本知识,以及2)创造一种组织工程化手术解决方案来修复骨软骨缺陷。这些目标将通过两个特定的目标:1)使用MKK/MEK3基因敲除的转基因小鼠软骨细胞来构建和分析组织工程软骨;以及2)对关键信号通路(p38和JNK Mark)的药物抑制,这些信号通路调节组织工程软骨中软骨细胞蛋白多糖和胶原的沉积。分析将包括机械特性、胶原蛋白、交联物和GAG含量、多光子显微镜和组织的数学模型。该提案的目标与NIH和NIAMS的任务相关。功能工程化软骨将极大地减轻软骨损伤,影响约10%的人口(1)。获得有关软骨新基质形成的遗传决定因素的信息将增加对类风湿性关节炎和骨关节炎软骨退化的了解。这项建议包括组织工程、多光子成像和数学建模组件,是一项多学科努力,旨在促进疾病和修复过程中软骨细胞遗传编程的基本知识。从被敲除和突变了肿瘤坏死因子-α和白介素1-β信号元件的小鼠的软骨细胞将被收获,并种植在藻酸盐支架中,以促进新基质的形成。组织机械性能、胶原蛋白、蛋白多糖和交联物含量将在正常和转基因表型的培养过程中进行评估,并对相同的信号通路进行或不进行药物抑制,以影响细胞外基质的产生[2]。多光子成像将用于评估胶原沉积和网络结构(使用来自二次谐波的信号)和胶原交联物的形成(通过双光子自发荧光信号)。来自组织工程软骨的数据将适用于软骨生长混合模型,该模型以前开发用于评估本地软骨(3)。每年,软骨损伤影响到近100万美国人,导致20万人接受手术。损伤常常隐蔽地导致骨关节炎(1)。组织工程软骨是研究软骨细胞控制的软骨降解和修复的一种很有前途的方法。了解这些体外过程将有助于临床医生通过药物、遗传和外科操作来控制和修复软骨。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Christopher B Raub其他文献
Christopher B Raub的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Christopher B Raub', 18)}}的其他基金
A high throughput, in vitro screening system for treatments of oral mucositis in cancer
用于治疗癌症口腔粘膜炎的高通量体外筛选系统
- 批准号:
10041746 - 财政年份:2020
- 资助金额:
$ 5.22万 - 项目类别:
A high throughput, in vitro screening system for treatments of oral mucositis in cancer
用于治疗癌症口腔粘膜炎的高通量体外筛选系统
- 批准号:
10251272 - 财政年份:2020
- 资助金额:
$ 5.22万 - 项目类别:
A dual-modality quantitative phase and polarized light microscope to assess cell motility and extracellular matrix remodeling during invasion
双模态定量相和偏光显微镜评估侵袭过程中的细胞运动和细胞外基质重塑
- 批准号:
9924599 - 财政年份:2019
- 资助金额:
$ 5.22万 - 项目类别:
Controlling chondrocyte matrix degradation and repair in 3-D culture.
控制 3D 培养中的软骨细胞基质降解和修复。
- 批准号:
7807636 - 财政年份:2010
- 资助金额:
$ 5.22万 - 项目类别:
Controlling chondrocyte matrix degradation and repair in 3-D culture.
控制 3D 培养中的软骨细胞基质降解和修复。
- 批准号:
8035903 - 财政年份:2010
- 资助金额:
$ 5.22万 - 项目类别:
Multiphoton Imaging and Rheology of Fibrosis Models
纤维化模型的多光子成像和流变学
- 批准号:
7407804 - 财政年份:2007
- 资助金额:
$ 5.22万 - 项目类别:
Multiphoton Imaging and Rheology of Fibrosis Models
纤维化模型的多光子成像和流变学
- 批准号:
7496521 - 财政年份:2007
- 资助金额:
$ 5.22万 - 项目类别:
相似海外基金
Probe-type nanowire sensor for label-free, in-situ, ultrasensitive detection of biomarkers from single cell in adherent culture
探针型纳米线传感器,用于无标记、原位、超灵敏地检测贴壁培养中单细胞的生物标志物
- 批准号:
21K14653 - 财政年份:2021
- 资助金额:
$ 5.22万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
CAREER: Rolled Scaffold for High-Density Adherent Culture of Mammalian Cells
职业:用于哺乳动物细胞高密度贴壁培养的滚动支架
- 批准号:
1848251 - 财政年份:2019
- 资助金额:
$ 5.22万 - 项目类别:
Continuing Grant