Targeting Cellular Mechanosensing to Alleviate Joint Stiffness in Synovial Fibrosis
靶向细胞机械传感减轻滑膜纤维化引起的关节僵硬
基本信息
- 批准号:10657546
- 负责人:
- 金额:--
- 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:2022-08-01 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAreaArthralgiaAttenuatedBehaviorBiochemicalBiophysicsCartilageCell Differentiation processCell NucleusCellsContractureCuesCytoskeletonDataDegenerative polyarthritisDepositionDevelopmentDiseaseDrug Delivery SystemsDrug TargetingElementsEnvironmentEpigenetic ProcessExposure toExtracellular MatrixFibroblastsFibrosisGeneral PopulationGoalsHomeostasisHumanImmobilizationIn VitroIncidenceIncubatedInjuryInterventionJointsKidneyKnowledgeLiverLubricantsLungMechanicsMediatingMediatorMemoryMicrospheresMilitary PersonnelModelingMovementMyofibroblastOperative Surgical ProceduresOrganOryctolagus cuniculusPathologyPathway interactionsPatientsPharmaceutical PreparationsPhenotypePopulationPrevalenceProteinsRegulationResearchRoleScienceSignal TransductionSourceSurfaceSynovial CellSynovial FluidSynovial MembraneTestingTimeTissuesTranscriptional Coactivator with PDZ-Binding MotifTransforming Growth Factor betaUnited StatesVeteransWorkactive dutyarticular cartilagebody systemcell behaviorcellular targetingchondroprotectioncytokinedisabilitydruggable targetend stage diseaseexperiencefasudilfunctional restorationinnovationjoint destructionjoint functionjoint injuryjoint stiffnessknee replacement arthroplastylubricinmechanotransductionmicrosphere deliverymilitary veteranpatient populationsmall moleculesmall molecule therapeuticstherapeutic targettranscription factortreatment strategy
项目摘要
Joint pain and stiffness associated with osteoarthritis and synovial fibrosis affects a large population of active
duty military and veterans with an incidence higher than the general public. Despite the prevalence of disease,
there are currently no non-surgical treatments with significant disease-modifying capabilities, and consequently
end stage disease culminates in total knee arthroplasty. The research goal of this proposal is to develop and
test a non-surgical intervention to alleviate joint stiffness and protect the joint’s cartilage surfaces. In synovial
fibrosis, fibroblast to myofibroblast differentiation leads to joint stiffening via cell-mediated extracellular matrix
deposition and reorganization. Additionally, this fibrotic differentiation of synovial fibroblasts leads to reduced
lubricant secretion into the synovial fluid. Mechanosensing, or a cell’s interpretation of the mechanical
microenvironment, is a crucial facet of fibrosis development and may potentially pose a therapeutic target. In this
proposal, we will target synovial cell contractility, or how much a cell pulls on its local environment, to introduce
a therapy that can both mitigate fibrotic cell differentiation and restore lubricant expression in joints. We will test
our hypothesis that modulating cellular mechanosensing can inhibit synovial fibrosis using two Aims. In the first
Aim, we will assess how a microsphere-delivered small molecule, fasudil, can inhibit fibrotic behaviors of synovial
fibroblasts collected from total knee arthroplasty patients. In the second Aim, we will assess this treatment using
a rabbit model of synovial fibrosis induced via joint injury and immobilization. This Aim will test two treatment
strategies by introducing the treatment in the incubation periods of disease following injury and also after the
onset of fibrosis at the time of remobilization. Overall, this work has the potential to introduce a new treatment
option for veterans experiencing joint pain and stiffness that can delay the need for surgical intervention.
关节疼痛和僵硬与骨关节炎和滑膜纤维化有关,影响大量活跃人群
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)
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Carla Rose Scanzello其他文献
Carla Rose Scanzello的其他文献
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{{ truncateString('Carla Rose Scanzello', 18)}}的其他基金
Achieving Sustained Control of Inflammation to Prevent Post-Traumatic Osteoarthritis (PTOA)
实现炎症的持续控制以预防创伤后骨关节炎 (PTOA)
- 批准号:
10641225 - 财政年份:2023
- 资助金额:
-- - 项目类别:
BCCMA: Cartilage Repair Strategies to Alleviate Arthritis Pain (Care AP): Targeting Pattern-Recognition to Reduce Pain-Related Pathology in Osteoarthritis
BCCMA:缓解关节炎疼痛的软骨修复策略(Care AP):以模式识别为目标,减少骨关节炎中与疼痛相关的病理
- 批准号:
10620628 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Targeting Cellular Mechanosensing to Alleviate Joint Stiffness in Synovial Fibrosis
靶向细胞机械传感减轻滑膜纤维化引起的关节僵硬
- 批准号:
10475464 - 财政年份:2022
- 资助金额:
-- - 项目类别:
BCCMA: Cartilage Repair Strategies to Alleviate Arthritis Pain (Care AP): Targeting Pattern-Recognition to Reduce Pain-Related Pathology in Osteoarthritis
BCCMA:缓解关节炎疼痛的软骨修复策略(Care AP):以模式识别为目标,减少骨关节炎中与疼痛相关的病理
- 批准号:
10365346 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Modulation of Inflammation in Osteoarthritis via CD14-mediated pattern recognition
通过 CD14 介导的模式识别调节骨关节炎炎症
- 批准号:
10224102 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Modulation of Inflammation in Osteoarthritis via CD14-mediated pattern recognition
通过 CD14 介导的模式识别调节骨关节炎炎症
- 批准号:
10450671 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Modulation of Inflammation in Osteoarthritis via CD14-mediated pattern recognition
通过 CD14 介导的模式识别调节骨关节炎炎症
- 批准号:
10052718 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Modulation of Inflammation in Osteoarthritis via CD14-mediated pattern recognition
通过 CD14 介导的模式识别调节骨关节炎炎症
- 批准号:
10669024 - 财政年份:2020
- 资助金额:
-- - 项目类别:
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