Achilles Tendinopathy Center of Research Translation

跟腱病研究翻译中心

• 批准号: 10403252
• 负责人: LOUIS J SOSLOWSKY
• 金额: $ 156.12万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10403252
• 关键词: Address; Adjuvant; Animal Model; Animals; Ankle; Architecture; Area; Back; Basic Science; Biological; Biological Models; Biopsy; Cell Nucleus; Cells; Center for Translational Science Activities; Clinical; Clinical Data; Clinical Treatment; Communication; Communities; Cytoskeleton; Data; Development; Disease; Disease Progression; Elements; Etiology; Fostering; Frequencies; Genome; Goals; Grant; Homeostasis; Human; Intervention; Knowledge; Length; Measurement; Mechanics; Modality; Modeling; Monitor; Onset of illness; Operative Surgical Procedures; Outcome; Pain; Pathogenesis; Patients; Pattern; Pennsylvania; Phenotype; Population; Positioning Attribute; Prevalence; Process; Regimen; Regulation; Rehabilitation therapy; Research; Research Project Grants; Resources; Role; Scientist; Signal Pathway; Societies; Source; Specimen; Surgeon; Technology; Tendinopathy; Tendon structure; Therapeutic Intervention; Tissues; Translating; Translational Research; Translations; Universities; Work; achilles tendon; chromatin remodeling; clinical translation; cost; design; disability; effective therapy; epigenetic regulation; foot; human subject; human tissue; improved; innovation; insight; interest; mechanical force; mechanical load; multidisciplinary; novel; novel therapeutic intervention; novel therapeutics; older patient; programs; small molecule; superresolution imaging; tendon development; tool; translational scientist

Abstract The Achilles Tendinopathy Center of Research Translation (AT-CORT) at the University of Pennsylvania will foster fundamental discoveries to guide clinical translation, as well as develop and employ novel translational resources, models and technologies, to address the highly significant research and clinical challenge of Achilles tendinopathy. Despite the high frequency and increasing prevalence of tendinopathy in young and old patients, and the significant pain and disability that arises from this condition, as well as the associated high cost to society, effective treatment modalities have stagnated over the last two decades. This is due to the lack of fundamental understanding of tendon disease etiology and pathogenesis, which limits development of novel treatment modalities. At present, beyond surgical intervention for late-stage disease, the only approved clinical therapy involves physical interventions via controlled rehabilitation mechanical loading of the tendon. While efficacious in some patients, outcomes of this intervention do not stem disease progression in most patients. Given the central mechanical role of the Achilles tendon, and the critical role of mechanical loading and mechanobiology on tendon cell homeostasis, it is critical that we develop and expand our understanding of the role of mechanical forces in disease onset and progression to optimize existing and inform new treatment strategies. Our proposed AT-CORT is uniquely positioned with a critical mass of multidisciplinary scientists and clinicians with strong interest and expertise in these and related areas. The Overall goal of the AT-CORT is to develop new insight and technologies that uncover the mechanobiologic basis of Achilles tendinopathy across length scales, from the nucleus, to the cell, to the tissue microenvironment to patients. We will assess these critical elements during disease onset and progression, informed by both vivo animal models that replicate disease processes and source material and real-world loading data from living human subjects. The AT-CORT is comprised of four independent and yet interactive elements, including an Administrative Core to oversee and guide interactions and primary Research Projects focused on the transfer of information from the external tendon cell microenvironment through the cytoskeleton (Project 1) and on chromatin remodeling and mechano-epigenetic regulation of tendon cell phenotype (Project 2). Using cells, tissue, and loading information derived from both human and animal tendinopathic models (Tissue Core), these research projects will advance our knowledge of the origins of tendinopathic disease and define new avenues for therapeutic intervention. Together, our highly interdisciplinary team, innovative tools, and outstanding and interactive Research Projects and Cores will dramatically advance knowledge, develop innovative tools and insight, and provide new directions for translation of novel therapies to treat Achilles tendinopathy.

摘要 宾夕法尼亚大学的跟腱病研究翻译中心（AT-CORT）将 促进基础发现，以指导临床翻译，以及开发和采用新的翻译 资源、模型和技术，以应对阿基里斯高度重要的研究和临床挑战 肌腱病尽管肌腱病在年轻和老年患者中的发生率很高且患病率不断增加， 以及由此引起的严重疼痛和残疾，以及相关的社会高昂成本， 过去二十年来，有效的治疗方式停滞不前。这是因为缺乏基本的 对肌腱疾病病因和发病机制的了解，限制了新治疗方法的开发 方式。目前，除了晚期疾病的手术干预外， 涉及通过肌腱的受控康复机械负荷的物理干预。虽然有效 在一些患者中，这种干预的结果并不能阻止大多数患者的疾病进展。鉴于 跟腱的中心机械作用，以及机械负荷和机械生物学的关键作用 对于肌腱细胞内稳态，我们发展和扩大对机械性 在疾病的发生和发展的力量，以优化现有的和新的治疗策略。我们提出的 AT-CORT具有独特的优势，拥有大量多学科科学家和临床医生， 在这些领域和相关领域的兴趣和专门知识。AT-CORT的总体目标是开发新的洞察力 和技术，揭示了跟腱病的机械生物学基础，从长度尺度， 从细胞核到细胞，再到患者的组织微环境。我们将评估这些关键因素， 疾病发作和进展，由复制疾病过程的体内动物模型和 源材料和真实世界的加载数据从生活的人类受试者。AT-CORT由四个 独立但互动的要素，包括监督和指导互动的行政核心 主要研究项目集中在从外部肌腱细胞的信息传递 微环境通过细胞骨架（项目1）和染色质重塑和机械表观遗传 肌腱细胞表型的调节（项目2）。使用细胞、组织和来自两者的载荷信息， 人类和动物肌腱病变模型（组织核心），这些研究项目将推进我们的知识， 肌腱病的起源，并确定新的治疗干预的途径。在一起，我们高度 跨学科的团队，创新的工具，优秀的和互动的研究项目和核心将 大幅提升知识，开发创新工具和洞察力，并为翻译提供新的方向 治疗跟腱病的新疗法