Mechanical Regulation of Cell Fate and Multi-Scale Function in the Developing Meniscus
半月板发育中细胞命运和多尺度功能的机械调节
基本信息
- 批准号:10359683
- 负责人:
- 金额:$ 51.85万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-04-01 至 2024-02-29
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultBackCell Differentiation processCell ExtractsCell Fate ControlCell physiologyCellsCuesCustomData SetDense Connective TissueDeteriorationDevelopmentDevicesEnvironmentEvaluationExcisionExtracellular MatrixExtracellular Matrix ProteinsFeedsFosteringFunctional RegenerationHeterogeneityIn SituIn Situ HybridizationInjuryInterventionJointsKneeKnowledgeLabelLasersMechanicsMeniscus structure of jointMicrofluidicsMotionMusNaturePatientsPhenotypePhysical environmentPlayPopulationProcessPropertyProtein-Lysine 6-OxidaseRegulationReporterRoleSeriesStructureStructure-Activity RelationshipSynovial jointSystemTechniquesTestingTimeTissuescartilaginouscrosslinkhealinginsightjoint loadingmechanical forcemechanical propertiesmechanical signalmeniscus injurymouse modelnovelprogenitorregenerativeregenerative approachresidenceresponsesciatic nervestem cells
项目摘要
Abstract
The meniscus plays a vital role in healthy knee function. However, given the centrality of this tissue in load
transfer and the demanding physical environment, injury is common and healing in adults is limited. The
current lack of regenerative solutions for knee meniscus injury arises, in part, from the significant gap in our
understanding of the cellular origins and regulation of meniscus tissue during development. While it is well
appreciated that the meniscus arises from a specialized progenitor cell population that first defines the forming
synovial joint (interzone cells), the regulation and timing of the differentiation of these cells, their phenotypic
heterogeneity, the type and timing of matrix that these cells produce within defined intervals, how this matrix
matures and feeds back to influence cell function and fate, and the role of active mechanical forces (that begin
during the first stages of joint motion), remain poorly understood. To address these limitations, this proposal
uses a series of novel mouse models and micro-scale experimental techniques to investigate the origin and
track the fate and function of cells that comprise the mature meniscus. We will also define the time-evolving
structural and mechanical features of the developing matrix, and query the role of joint loading and cellular
response to mechanical inputs in this developmental paradigm. Our central hypothesis is that a common pool
of meniscal progenitor cells arises from the interzone, that these cells are acted on by microenvironmental
cues defined by early matrix assembly and active mechanical signals (that arise with joint loading), and that
these inputs act together to refine and direct meniscus maturation, enabling its adult function.
摘要
半月板在健康的膝关节功能中起着至关重要的作用。然而,考虑到该组织在负载中的中心位置,
由于交通和苛刻的物理环境,受伤是常见的,成年人的愈合是有限的。的
目前缺乏膝关节半月板损伤的再生解决方案,部分原因是我们在这方面的巨大差距。
了解细胞起源和半月板组织在发育过程中的调节。虽然它是好的
应当理解,半月板起源于特化的祖细胞群,其首先限定了半月板的形成。
滑膜关节(间区细胞),这些细胞分化的调节和时机,它们的表型
异质性,这些细胞在规定的时间间隔内产生的基质的类型和时间,
成熟并反馈影响细胞功能和命运,以及主动机械力的作用(开始
在关节运动的第一阶段),仍然知之甚少。为了克服这些局限性,本提案
使用一系列新颖的小鼠模型和微型实验技术来研究起源,
跟踪组成成熟半月板的细胞的命运和功能。我们还将定义时间演变
结构和力学特征的发展矩阵,并查询联合加载和细胞的作用
对机械输入的反应。我们的核心假设是,
这些细胞受到微环境的作用,
由早期矩阵组装和主动机械信号(随关节载荷而产生)定义的提示,
这些输入共同作用以改善和指导半月板成熟,使其能够发挥成年功能。
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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{{ truncateString('EIKI KOYAMA', 18)}}的其他基金
Evaluation of Prg4 as a New Therapy for TMJ Disc Degeneration
Prg4 作为 TMJ 椎间盘退变新疗法的评估
- 批准号:
10525000 - 财政年份:2022
- 资助金额:
$ 51.85万 - 项目类别:
Evaluation of Prg4 as a New Therapy for TMJ Disc Degeneration
Prg4 作为 TMJ 椎间盘退变新疗法的评估
- 批准号:
10677033 - 财政年份:2022
- 资助金额:
$ 51.85万 - 项目类别:
Mechanical Regulation of Cell Fate and Multi-Scale Function in the Developing Meniscus
半月板发育中细胞命运和多尺度功能的机械调节
- 批准号:
9903234 - 财政年份:2019
- 资助金额:
$ 51.85万 - 项目类别:
Mechanical Regulation of Cell Fate and Multi-Scale Function in the Developing Meniscus
半月板发育中细胞命运和多尺度功能的机械调节
- 批准号:
10589080 - 财政年份:2019
- 资助金额:
$ 51.85万 - 项目类别:
Mechanical Regulation of Cell Fate and Multi-Scale Function in the Developing Meniscus
半月板发育中细胞命运和多尺度功能的机械调节
- 批准号:
9764868 - 财政年份:2019
- 资助金额:
$ 51.85万 - 项目类别:
Mechanisms of TMJ development and long-term function
颞下颌关节发育和长期功能的机制
- 批准号:
8887326 - 财政年份:2014
- 资助金额:
$ 51.85万 - 项目类别:
Mechanisms of TMJ development and long-term function
颞下颌关节发育和长期功能的机制
- 批准号:
8614830 - 财政年份:2014
- 资助金额:
$ 51.85万 - 项目类别:
Pathogenic Mechanisms in Hereditary Multiple Exostoses Syndrome
遗传性多发性外生骨疣综合征的发病机制
- 批准号:
8475565 - 财政年份:2011
- 资助金额:
$ 51.85万 - 项目类别:
Pathogenic Mechanisms in Hereditary Multiple Exostoses Syndrome
遗传性多发性外生骨疣综合征的发病机制
- 批准号:
8294622 - 财政年份:2011
- 资助金额:
$ 51.85万 - 项目类别:
Pathogenic Mechanisms in Hereditary Multiple Exostoses Syndrome
遗传性多发性外生骨疣综合征的发病机制
- 批准号:
8183318 - 财政年份:2011
- 资助金额:
$ 51.85万 - 项目类别:
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