NIAMS: CORT Innovations to Assess and Forestall Post-Traumatic Osteoarthritis

爱荷华州大学CORT的目标是通过基础科学、生物工程、成像和临床研究等多学科转化方法，开发预防创伤后骨关节炎（PTOA）的新方法。中心主题是关节损伤引发一系列导致PTOA的生物学事件，并且关节损伤的新治疗方法将最大限度地减少这些有害事件并促进关节愈合。具体目标是：1）推进对PTOA发病机制的理解，2）开发和完善关节损伤严重程度的可靠定量测量，包括结构损伤和对关节损伤的生物反应的测量，以及3）将PTOA发病机制的理解和关节损伤评估的进展应用于预防PTOA的新方法。这四个CORT项目是：1。软骨细胞外基质碎片和创伤诱导的软骨溶解，一项体外研究，将确定负责损伤后细胞损伤传播的途径; 2. PTOA病因学中的急性与慢性机械损伤，这是一项实验研究，将定义受伤关节的负荷在导致OA中的作用，以及预防受伤关节OA的新方法; 3. MRI生物标志物在评估关节软骨健康中的验证和应用，这是一项非骨折软骨损伤的临床和实验研究，将有助于确定非侵入性措施评估软骨损伤严重程度的能力，将确定哪些急性关节损伤的滑液标志物反映了这种损伤，并将测试载荷降低加速受损关节表面恢复的假设;和4.量化损伤严重程度以评估创伤后OA的风险，这是一项关节内骨折的临床研究，将检验结构性关节损伤严重程度的新定量测量可预测临床结局的假设。该项目还将对关节损伤的严重程度进行多中心研究，为分子干预的临床试验做准备，以最大限度地降低关节损伤后OA的风险。这四个项目将由一个管理生物统计学核心，一个生物力学成像核心，以及一个组织和实验建模核心支持。

The goal of the University of Iowa CORT is to develop new methods of forestalling post-traumatic osteoarthritis (PTOA) through a multi-disciplinary translational approach including basic science, bioengineering, imaging, and clinical research. The central theme is that joint injuries initiate a sequence of biologic events that lead to PTOA and that new treatments of joint injuries will minimize these deleterious events and promote joint healing. The specific aims are to: 1) advance understanding of the pathogenesis of PTOA, 2) develop and refine reliable quantitative measures of severity of joint injuries, including measures of structural damage and biologic response to joint injury, and 3) apply the advances in understanding of the pathogenesis of PTOA and assessment of joint injury to new methods of forestalling PTOA. The four CORT projects are: 1. Cartilage Extracellular Matrix Fragments and Trauma-Induced Chondrolysis, an in vitro study that will identify pathways responsible for propagation of cell damage following injury; 2. Acute versus Chronic Mechanical Damage in the Etiology of PTOA, an experimental study that will define the role of loading of injured joints in causing OA, and new methods for preventing OA in injured joints; 3. Validation and Application of MRI Biomarkers in Assessing Articular Cartilage Health, a clinical and experimental study of non-fracture cartilage injury that will help define the ability of non-invasive measures to assess the severity of cartilage damage, that will identify which synovial fluid markers of acute joint injury reflect that damage, and that will test the hypothesis that decreased loading accelerates restoration of injured joint surfaces; and 4. Quantifying Injury Severity to Assess the Risk for Post-Traumatic OA, a clinical study of intra-articular fractures that will examine the hypothesis that new quantitative measures of the severity of structural joint injury predict clinical outcomes. This project also will conduct a multi-center study of the severity of joint injury, in preparation for clinical trials of molecular interventions to minimize the risk of OA following joint injury. The four projects will be supported by an administrative-biostatistics core, a biomechanics-imaging core, and a tissue and experimental modeling core.