New Approaches to Assess and Forestall Osteoarthritis in Injured Joints

描述(由申请人提供)：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换方法，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了一系列导致PTOA的生物事件，关节损伤的新治疗方法将使这些有害事件降至最低，并促进关节愈合。其具体目的是：1)提高对PTOA发病机制的认识；2)发展和完善可靠的关节损伤严重程度量化指标，包括结构损伤和对关节损伤的生物反应；3)将对PTOA发病机制和关节损伤评估的研究进展应用于预防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，这是一项体外研究，将确定损伤后细胞损伤的传播途径；2.PTOA病因学中的急性和慢性机械损伤，一项将确定损伤关节负荷在引起OA中的作用的实验研究，以及预防损伤关节中OA的新方法；3.MRI生物标记物在评估关节软骨健康中的验证和应用，这是一项关于非骨折软骨损伤的临床和实验研究，它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，并将检验减少负荷加速受损关节表面恢复的假设；以及4.量化损伤严重程度以评估创伤后骨性关节炎的风险，这是一项针对关节内骨折的临床研究，将检验以下假设：结构性关节损伤严重程度的新量化测量将预测临床结果。该项目还将对关节损伤的严重程度进行多中心研究，为将关节损伤后的骨性关节炎风险降至最低的分子干预临床试验做准备。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以及一个组织和实验建模核心提供支持。 与公共卫生相关：骨关节炎(OA)是最常见的关节疾病，也是导致疼痛、残疾和经济损失的最重要原因之一。大约12%的骨性关节炎发生在关节创伤之后。在许多常见的关节损伤后，骨关节炎的风险从20%到50%或更高；尽管治疗关节损伤的外科方法不断发展，但在过去20年中，这种风险并没有明显降低。这项CORT的基础科学、生物工程和临床研究将带来新的生物学和改进的关节损伤微创手术治疗，将预防OA，从而改善数十万人的生活。

DESCRIPTION (provided by applicant): 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. Relevance to Public Health: Osteoarthritis (OA) is the most common joint disease and is among the most important causes of pain, disability, and economic loss. About 12% of OA arises following joint trauma. The risk of OA ranges from 20% to 50% or more following many common joint injuries; and, despite evolving surgical methods of treating joint injuries, this risk has not decreased appreciably in the last 20 years. The basic science, bioengineering and clinical research in this CORT will lead to new biologic and improved minimally invasive operative treatments of joint injury that will forestall OA and thereby improve the lives of hundreds of thousands of people.