Multiscale tendon damage and aberrant cellular responses in an in vivo model of tendinosis
肌腱变性体内模型中的多尺度肌腱损伤和异常细胞反应
基本信息
- 批准号:10343017
- 负责人:
- 金额:$ 49.09万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-08-22 至 2027-07-31
- 项目状态:未结题
- 来源:
- 关键词:AblationActinsAcuteAnimal ModelArchitectureAreaAutomobile DrivingCell CommunicationCell DensityCell ShapeCellsChronicClinicalClinical ResearchCollagenCollagen FiberCollagen Type IIICytoskeletonDataDiseaseExhibitsF-ActinFiberFoundationsGoalsHumanImageInterventionKnowledgeMeasuresMechanicsModelingModulusMolecularNatural regenerationOutcomePainPhenotypePhysiological ProcessesPhysiologyPositioning AttributeProductionProteinsProteoglycanRattusRehabilitation therapyRoleSignal TransductionSlideStudy modelsTendinopathyTendon structureTestingTimeTissuesTropomyosinachilles tendondepolymerizationdesignfiber cellin vivoin vivo Modelmechanical loadmechanical propertiesmechanical signalmechanotransductionmolecular scalenanoscalenovelpolymerizationpre-clinicalpreventresponsetherapy designtransmission process
项目摘要
Project Summary
Tendon overuse initiates mechanical damage that leads to chronic tendinosis (degeneration) and
tendinopathy (clinical presentation with pain), which are common and notoriously difficult to treat. Despite the
widely accepted role of loading in tendinosis, the structural, mechanical, and cellular mechanisms by which
loading leads to initiation and progressive damage in tendinosis remain unknown. We hypothesize that
overload causes micro-scale structural and mechanical damage, which alters load transmission to
cells, driving the multi-scale structural and molecular progression of tendinosis in a vicious cycle.
To determine the mechanisms involved in tendinosis, a preclinical in vivo animal model of tendon
overuse and multiscale assessments of tendon structural and mechanical damage and interrogation of
cellular mechanotransduction and intracellular signaling mechanisms are all required. This is because
the physiological processes in tendinosis involve tissue-scale tendon loading that is transferred to the micro-,
nano-, and molecular-scale, where microstructural damage and cellular mechanotransduction signaling occurs.
Our team has recently established a model of tendinosis using rat synergist ablation (SynAb), where we
remove the Achilles tendon, which overloads the synergistic plantaris tendon without directly injuring it. Our
pilot data exhibit hallmark features of human tendinosis (increased area, collagen disorganization,
proteoglycan accumulation, collagen Type III production, and reduced tensile modulus).
Our long-term goal is to enable interventions for tendon regeneration and rehabilitation to treat tendinopathy
and prevent its progression. The objective of this proposal is to determine the mechanisms responsible
for onset and progression of tendinosis in the SynAb model of tendon overuse in the following aims:
Aim 1: Assess the multiscale structural changes following the onset and progression of tendinosis.
Aim 2: Quantify the multiscale mechanical properties and damage following the onset and progression
of tendinosis.
Aim 3: Interrogate changes in tenocyte mechanoresponse and cytoskeleton during tendon overload.
This study will determine the mechanisms responsible for the multiscale damage in overuse tendinosis and
establish these in the context of key hallmarks of human tendinosis using a preclinical in vivo model.
Quantifying multiscale damage and cellular mechanisms by which loading leads to tendinosis is critical for
designing and evaluating interventions to prevent and treat tendinopathy.
项目总结
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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DAWN M ELLIOTT其他文献
DAWN M ELLIOTT的其他文献
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{{ truncateString('DAWN M ELLIOTT', 18)}}的其他基金
Multiscale tendon damage and aberrant cellular responses in an in vivo model of tendinosis
肌腱变性体内模型中的多尺度肌腱损伤和异常细胞反应
- 批准号:
10687977 - 财政年份:2022
- 资助金额:
$ 49.09万 - 项目类别:
Delaware Center for Musculoskeletal Research, Administrative Supplement for Equipment
特拉华州肌肉骨骼研究中心,设备行政补充资料
- 批准号:
10591284 - 财政年份:2021
- 资助金额:
$ 49.09万 - 项目类别:
Delaware Center for Musculoskeletal Research - Wang
特拉华州肌肉骨骼研究中心 - 王
- 批准号:
10854179 - 财政年份:2021
- 资助金额:
$ 49.09万 - 项目类别:
Delaware Center for Musculoskeletal Research – Administrative Core
特拉华州肌肉骨骼研究中心 — 行政核心
- 批准号:
10091020 - 财政年份:2021
- 资助金额:
$ 49.09万 - 项目类别:
Delaware Center for Musculoskeletal Research – Administrative Core
特拉华州肌肉骨骼研究中心 — 行政核心
- 批准号:
10352302 - 财政年份:2021
- 资助金额:
$ 49.09万 - 项目类别:
Delaware Center for Musculoskeletal Research – Administrative Core
特拉华州肌肉骨骼研究中心 – 行政核心
- 批准号:
10885870 - 财政年份:2021
- 资助金额:
$ 49.09万 - 项目类别:
Delaware Center for Musculoskeletal Research – Administrative Core
特拉华州肌肉骨骼研究中心 – 行政核心
- 批准号:
10782401 - 财政年份:2021
- 资助金额:
$ 49.09万 - 项目类别:
Simulating Workforce Design Teams in Biomedical Engineering Education
模拟生物医学工程教育中的劳动力设计团队
- 批准号:
10204530 - 财政年份:2021
- 资助金额:
$ 49.09万 - 项目类别:
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