Translating Molecular Signal Pathways to Orthopaedic Trauma Care

将分子信号通路转化为骨科创伤护理

• 批准号: 8893754
• 负责人: Edward M. Schwarz
• 金额: $ 8.29万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8893754
• 关键词: Adjuvant; Affect; Aging; Allografting; Anabolic Agents; Anatomy; Bone Injury; Bone Regeneration; Canis familiaris; Cells; Clinical; Collaborations; Degenerative polyarthritis; Disease; Elderly; Event; Fracture; Generations; Goals; Human; Image; In Vitro; Incidence; Injury; Joints; Manuscripts; Modeling; Molecular; Musculoskeletal; Musculoskeletal Diseases; Orthopedics; Patients; Pilot Projects; Pre-Clinical Model; Recording of previous events; Research; Research Infrastructure; Resources; Role; Signal Pathway; Signal Transduction; Stem cells; Teriparatide; Therapeutic; Tissues; Translating; Translational Research; Universities; articular cartilage; base; design; effective therapy; experience; human tissue; in vivo; injury and repair; innovation; joint injury; musculoskeletal injury; novel; progenitor; programs; protective effect; repaired; research facility; response; skeletal injury; success; tissue regeneration; tissue repair; trauma care

The CORT Program was initiated in 2006 and has had a transformative impact on the musculoskeletal research program at the University of Rochester. The Program has focused the collective efforts of an experienced, talented, and multi-disciplinary research team. The objective of the CORT Program is to translate understanding of the molecular, cellular and tissues responses involved in musculoskeletal injury into novel therapies for tissue regeneration and repair. The scientific basis of the CORT program is that injury and repair responses are fundamentally dependent upon the ability of stem cell progenitors to undergo proliferation and expansion, and subsequent tissue specific differentiation. The unifying theme of the CORT Program is that PTH is a key anabolic agent that promotes tissue-specific MSC expansion and repair events. The CORT renewal application continues a Program designed to transform the treatments of two major musculoskeletal diseases, 1) skeletal injury and 2) joint injury/osteoarthritis. Both diseases have a higher incidence and greater affect on the elderly. The CORT program has stimulated scientific discoveries resulting in the generation of 61 manuscripts. Project 1, "Teriparatide as a Therapy for Osteoarthritis Following Meniscal Injury" uses in vivo and in vitro preclinical models and human tissues and cells to define the mechanism involved in the chondro-protective effect of PTH on articular cartilage. Project 2, "Role of PTH in Enhancing Fracture Repair in Aging" defines the downstream signals and targets that PTH activates and which are necessary for the stimulation of bone repair. Project 3: "Translating PTH Therapy as an Adjuvant for Structural Allografting" expands the translational scope of the CORT by examining the therapeutic potential of PTH in bone repair in a canine model and includes a human clinical pilot study. The projects are supported by an Administrative Core that enhances collaborations and integration with the institutional CTSI and research base, and an innovative and comprehensive Molecular and Anatomic Imaging Core. The Program has the entire constellation of factors necessary for success, including: i) a collaborative research team; ii) an exceptional research infrastructure that permits comprehensive experimental approaches; iii) a history of scientific innovation and commitment to translational research; iv) excellent integration of and access to institutional research resources and facilities by a talented research team.

Cort计划始于2006年，对罗切斯特大学的肌肉骨骼研究计划产生了变革性的影响。该计划重点是经验丰富，有才华和多学科研究团队的集体努力。 CORT计划的目的是转化对肌肉骨骼损伤涉及的分子，细胞和组织反应的理解，以进行新型的组织再生和修复疗法。科特计划的科学基础是，损伤和修复反应从根本上取决于干细胞祖细胞进行增殖和扩张的能力，以及随后的组织特定分化。 Cort计划的统一主题是PTH是促进组织特异性MSC扩展和修复事件的关键合成代谢剂。 CORT更新应用程序继续进行一项计划，旨在改变两种主要肌肉骨骼疾病的治疗方法，1）骨骼损伤和2）关节损伤/骨关节炎。两种疾病的发生率都更高，对老年人的影响更大。 Cort计划激发了科学发现，导致了61个手稿。项目1，“半月板损伤后的teriparatide作为骨关节炎的治疗”在体内和体外临床前模型以及人体组织和细胞中使用了PTH对关节软骨的软骨保护作用所涉及的机制。项目2，“ PTH在增强衰老中断裂修复中的作用”定义了PTH激活PTH的下游信号和目标，而这些信号是刺激骨骼修复所必需的。项目3：“将PTH疗法翻译为结构同种异体的佐剂”，通过检查犬模型中PTH的治疗潜力来扩大Cort的翻译范围，并包括人类的临床试验研究。这些项目得到了行政核心的支持，该核心增强了与机构CTSI和研究基础的协作和集成，以及创新，全面的分子和解剖成像核心。该计划具有成功所必需的整个因素，包括：i）协作研究团队； ii）一种允许全面实验方法的杰出研究基础设施； iii）科学创新和对翻译研究的承诺的历史； iv）才华横溢的研究团队可以很好地整合和访问机构研究资源和设施。