RI COBRE: ASSESSMENT OF CHONDROPROTECTION IN ACL INJURIES

RI COBRE：ACL 损伤中软骨保护的评估

• 批准号: 7610824
• 负责人: GREGORY D. JAY
• 金额: $ 34.05万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-15 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7610824
• 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; Elevation; End Point; Failure; Friction; Funding; Grant; 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; lubricin

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. 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 nstruments. 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 populationbased 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 (u) 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.

该副本是利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，这不一定是调查员的机构。 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NStruments，几项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。我们认为急性膝盖受伤和导致的炎症患者面临早期磨损和关节损害的风险 由于润滑能力的丧失而导致软骨。这些患者出现在急诊室，表现出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。我们认为，炎症会导致润滑剂破坏，并伴随着软骨和慢性症状的纤维化，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最早因素的干预措施可能是急诊科（ED）或基于初级保健。关节损伤后，限制此过程的程度可能是主要治疗终点后，可能会立即有一个关键的时间窗口。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：ACL 大鼠膝关节引起的损伤导致润滑剂代谢变化，导致关节的摩擦系数升高。这会导致对铰接表面的永久损害或关节未能恢复为0.001的低M。目标2：通过给药阻断TNF-A的影响 TNF-A抑制剂部分恢复了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损伤患者的滑动流体对IL-1和TNF-A分析。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。