New Approaches to Assess and Forestall Osteoarthritis in Injured Joints

爱荷华大学CORT的目标是通过包括基础科学、生物工程、成像和临床研究在内的多学科转化方法，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生物事件，导致PTOA，而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)增进对上睑下垂发病机制的理解；2)开发和完善可靠的关节损伤严重程度定量测量，包括结构损伤和关节损伤的生物反应测量；3)将对上睑下垂发病机制的理解和关节损伤评估的进展应用于预防上睑下垂的新方法。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，这是一项体外研究，将确定损伤后细胞损伤传播的途径；2. 急性与慢性机械损伤在pta病因学中的作用，这是一项实验研究，将确定损伤关节的负荷在导致OA中的作用，以及预防损伤关节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，这是一项非骨折性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，这将确定急性关节损伤的滑液标记物反映了该损伤，并将验证载荷减少加速损伤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骨性关节炎的风险，这是一项关于关节内骨折的临床研究，该研究将检验结构性关节损伤严重程度的新定量测量方法预测临床结果的假设。本项目还将开展关节损伤严重程度的多中心研究，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行政-生物统计学核心、一个生物力学-成像核心和一个组织和实验建模核心提供支持。

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.