Translating Molecular Signal Pathways to Orthopaedic Trauma Care

CORT计划于2006年启动，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。该计划集中了一个经验丰富，才华横溢，多学科研究团队的集体努力。CORT计划的目标是将对肌肉骨骼损伤中所涉及的分子、细胞和组织反应的理解转化为组织再生和修复的新疗法。CORT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增以及随后的组织特异性分化的能力。CORT计划的统一主题是PTH是促进组织特异性MSC扩增和修复事件的关键合成代谢剂。CORT更新申请延续了旨在改变两种主要肌肉骨骼疾病治疗的计划，1）骨骼损伤和2）关节损伤/骨关节炎。这两种疾病的发病率较高，对老年人的影响也较大。CORT项目激发了科学发现，产生了61份手稿。项目1，“Teriparthrin作为半月板损伤后骨关节炎的治疗”使用体内和体外临床前模型以及人体组织和细胞来定义PTH对关节软骨的软骨保护作用所涉及的机制。项目2，“PTH在增强衰老中骨折修复中的作用”定义了PTH激活的下游信号和靶点，这些信号和靶点对于刺激骨修复是必要的。项目三：“将PTH疗法转化为结构性同种异体移植的佐剂”通过在犬模型中检查PTH在骨修复中的治疗潜力来扩展CORT的转化范围，并包括人类临床试点研究。这些项目得到了行政核心的支持，加强了与机构CTSI和研究基地的合作和整合，以及创新和全面的分子和解剖成像核心。该计划具有成功所需的全部要素，包括：i）合作研究团队; ii）允许综合实验方法的特殊研究基础设施; iii）科学创新和致力于转化研究的历史; iv）优秀的整合和获得机构研究资源和设施的人才研究团队。

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.