RI COBRE: ASSESSMENT OF CHONDROPROTECTION IN ACL INJURIES

RI COBRE：ACL 损伤中软骨保护的评估

• 批准号: 7959906
• 负责人: GREGORY D. JAY
• 金额: $ 15.31万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959906
• 关键词: Accident and Emergency department; Acute; Address; Anterior Cruciate Ligament; Aspirate substance; Cartilage; Centers of Research Excellence; Chronic; Clinical; Collagen Type II; Computer Retrieval of Information on Scientific Projects Database; Data Collection; Defect; Degenerative polyarthritis; Digestion; Failure; Friction; Funding; Grant; Health; Inflammation; Inflammatory; Injury; Institution; Interleukin-1; Intervention; Joints; Knee Injuries; Knee joint; Lubrication; Mediating; Metabolism; Pathogenesis; Patients; Play; Population Study; Primary Health Care; Process; Rattus; Recording of previous events; Research; Research Personnel; Resources; Risk; Risk Factors; Role; Secondary to; Source; Surface; Symptoms; Synovial Fluid; Synovitis; Therapeutic; Time; Trauma; United States National Institutes of Health; articular cartilage; base; cytokine; inhibitor/antagonist; instrument; joint injury; ligament injury; lubricin; population based; repaired; skeletal; Accident and Emergency department; Acute; Address; Anterior Cruciate Ligament; Aspirate substance; Cartilage; Centers of Research Excellence; Chronic; Clinical; Collagen Type II; Computer Retrieval of Information on Scientific Projects Database; Data Collection; Defect; Degenerative polyarthritis; Digestion; Failure; Friction; Funding; Grant; Health; Inflammation; Inflammatory; Injury; Institution; Interleukin-1; Intervention; Joints; Knee Injuries; Knee joint; Lubrication; Mediating; Metabolism; Pathogenesis; Patients; Play; Population Study; Primary Health Care; Process; Rattus; Recording of previous events; Research; Research Personnel; Resources; Risk; Risk Factors; Role; Secondary to; Source; Surface; Symptoms; Synovial Fluid; Synovitis; Therapeutic; Time; Trauma; United States National Institutes of Health; articular cartilage; base; cytokine; inhibitor/antagonist; instrument; joint injury; ligament injury; lubricin; population based; repaired; skeletal

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Loss of Lubrication and Enhanced Cartilage Wear in the Acute ACL Injury Injury is a well established risk factor in the pathogenesis of osteoarthritis (OA). Several large longitudinal population studies support this observation based upon patient history and retrospective data collection instruments. However, efforts to identify patients at risk of progression have been limited. We posit that patients with acute knee injuries and resultant inflammation are at risk for early wear and damage to articular cartilage due to loss of lubricating ability. These patients present to emergency departments and manifest an acute traumatic synovitis (TS) secondary to acute structural defects such as acute anterior cruciate ligament (ACL) injuries following trauma. These patients are young and feature, 1) collagen type II fragment release consistent with early cartilage destruction, 2) digestion of lubricin (PRG4) and lack lubricating ability, and 3) do not have any history of degenerative joint disease. We argue that inflammation results in the destruction of lubricin, accompanied by the fibrillation of cartilage and chronic symptoms which underpin the population based observation of early OA attributable to joint injury. Interventions intended to address some of the earliest causative factors of OA could be emergency department (ED) or primary care based. There may also be a critical time window immediately after a joint injury when limiting the extent of this process could be a primary therapeutic endpoint. The aims are the following: Aim 1: To Investigate the Early Effects of an ACL Injury on Lubricating Mechanisms Mediated by Lubricin in a Mammalian Joint. Hypothesis: An ACL injury induced in rat knee joints results in changes to lubricin metabolism leading to an elevation of the coefficient of friction (¿) of the joint. This results in permanent damage to articulating surfaces or failure of the joint to return to a low m of 0.001. Aim 2: Blocking the Effects of TNF-a Through the Administration of a TNF-a Inhibitor Partially Restores the Lubricating Ability of Diarthrodial Joints Following ACL Injury. Hypothesis: TNF-a play a significant role in mediating changes in lubricin metabolism following ACL injury. Blocking the effects of TNF-a preserves joint lubrication and limits joint wear. Aim 3: Synovial Fluid Aspirates from Patients with Acute ACL Injuries will be Analyzed for IL-1 and TNF-a. Hypothesis: An inverse relationship exists between lubricin concentration and catabolic cytokines in clinical aspirates which can be characterized as a mild inflammatory state.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 急性ACL损伤中润滑和软骨磨损的损失 损伤是骨关节炎（OA）发病机理中良好的危险因素。基于患者病史和回顾性数据收集工具，一些大型纵向人群研究支持了这一观察结果。但是，识别有进展风险的患者的努力受到限制。我们认为，由于失去润滑能力，急性膝盖损伤和导致感染的患者有可能早期磨损和关节软骨损害的风险。这些患者出现在紧急部门，表现出急性结构缺陷继发于急性结构缺陷的急性创伤性滑膜炎（TS），例如创伤后急性前交叉韧带（ACL）损伤。这些患者年轻，特征1）与早期软骨破坏一致的II型胶原蛋白片段释放，2）消化润滑剂（PRG4）（PRG4）和缺乏润滑能力，3）没有任何退行性关节疾病史。注射会导致润滑剂破坏，并伴随着软骨和慢性症状的纤颤，这些症状是基于人口的早期OA观察到的，归因于关节损伤。旨在解决OA最早的严重因素的干预措施可能是基于急诊科或初级保健。在限制此过程的程度时，可能会立即有一个关键的时间窗口 主要治疗终点。目的是：目标1：研究ACL损伤对哺乳动物关节中润滑剂介导的润滑机制的早期作用。假设：大鼠膝关节引起的ACL损伤导致润滑剂代谢的变化，导致关节的批判摩擦升高。这导致对铰接表面或故障的永久损害 关节返回到0.001的低m。 AIM 2：通过施用TNF-A抑制剂阻止TNF-A的影响部分恢复了ACL损伤后腹膜关节的润滑能力。假设：TNF-A在ACL损伤后介导润滑剂代谢的变化中起着重要作用。阻止TNF-A的影响可保留关节润滑并限制关节磨损。 AIM 3：将分析来自急性ACL损伤患者的滑液抽吸的IL-1和TNF-A。假设：在临床抽吸物中，润滑剂浓度与分解代谢细胞因子之间存在反比关系，这可以被描述为轻度炎症状态。