Function and Behavior Phenotype of Inflammatory Arthritis in the Rat Knee and TMJ

大鼠膝关节和颞下颌关节炎症的功能和行为表型

• 批准号: 8329660
• 负责人: Kyle D Allen
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-07 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8329660
• 关键词: Adult; Affect; Arthralgia; Arthritis; Award; Behavior; Behavioral; Biological; Bite; Bite Force; Bone remodeling; CCL2 gene; Cartilage; Cell Death; Chronic; Chronic Disease; Collaborations; Comorbidity; Cues; Data; Degenerative polyarthritis; Development; Diet; Diet Habits; Diet Records; Disease; Eating; Etiology; Event; Face; Fibroblasts; Fibrocartilages; Frequencies; Functional disorder; Future; Gait; Glycolysis; Goals; Grooming; Habits; Health; IL6 gene; IL8 gene; Inflammation; Inflammation Mediators; Inflammatory; Injection of therapeutic agent; Instruction; Intake; Intra-Articular Injections; Jaw; Jaw Diseases; Joints; Knee; Laboratory Rat; Length; Link; Liquid substance; Mastication; Measures; Mechanics; Mediator of activation protein; Methods; Metric; Minor; Modeling; Monitor; Musculoskeletal; National Institute of Dental and Craniofacial Research; Pain; Pathologic Processes; Pathology; Patients; Pattern; Phase; Phenotype; Population; Posture; Pre-Clinical Model; Process; Rattus; Regulation; Reporting; Research; Rheumatoid Arthritis; Rodent; Saliva; Serum; Simulate; Sleep; Sleep Apnea Syndromes; Sodium; Staging; Stimulus; Structure of trigeminal ganglion; Surface; Synovial Fluid; Synovial Membrane; System; Techniques; Temporomandibular Joint; Temporomandibular Joint Disorders; Temporomandibular Joint Dysfunction Syndrome; Temporomandibular joint arthritis; Testing; Time; Tooth structure; Training; Update; Withdrawal; Work; chronic pain; cost; design; design and construction; disability; drinking; end stage disease; experience; feeding; improved; inhibitor/antagonist; instrument; joint destruction; meter; orofacial; overexpression; statistics; tool

in degenerative joint diseases, the articiilating surfaces of a joint are gradually destroyed, ultimately resulting in pain and joint dysfunction. Most degenerative joint diseases are chronic pathologies: that are ¿ driven by disease processes occurring over years, and while end-stage disease can be described by cartilage loss, subchondral bone remodeling, dysfunction, and pain, the initiating stages do not always have a clear etiology. As a result, disease modifying strategies are faced with a diverse blend of chronic disease processes that have potentially risen from a number of cbhnplex origins. The goal of the ROO phase of this K99/R00 application is to Investigate local regulation of catabolic and pro-inflammatory mediators in the rat temporomandibular joint (TMJ) and the subsequent development of pain related behaviors and TMJ dysfunction. This work represents the transition of a K99/R00 award to the independent ROO phase. During K99 training, the PI investigated the local regulation of disease factors associated with knee arthritis and developed new quantitative gait measures of knee dysfunction for the rat pre-clinical model. In the ROO phase, a similar approach is proposed for the study of degenerative! pathology in the TMJ. First, we will develop new methods to assessib^haviors associated with TMJ pain and dysfunction in the rat, including new systems to assess chewing kjhematics, dietary habits,^ bite-force, sleeping and grooming behaviorSi and orofacial sensitivity. Concurrently, we will develop a model of chronic TMJ degeneration using ihtra-articular injection of sodium monoioddacetate (MIA); here, TMJ degeneration induced by MIA will occur over a period of weeks, simulating .the Chronic cascade of TMJ arthritis, in this model, we will investigate catabolic and pro-imflammatory rriarkers of TMJ pathology in thes serum, saliva, and TMJ synovial fluid. F'ihally, we will combine behavioral analysis tools with our model; of TMJ degeneration to examine tliei relatidnship between local regulation of disease processes and the development of disease sequelae associated with TMJ degeheration. With this work, we aim to identify critical features, stages,/and; mediators of TMJ degeheration with the goal of developing future interventional studies.

在退行性关节疾病中，关节的人工表面最终会逐渐被破坏。 导致疼痛和关节功能障碍。大多数退行性关节疾病都是慢性病理： 由多年来发生的疾病过程驱动，虽然终末期疾病可以通过 软骨丢失，软骨下骨改建，功能障碍和疼痛，初始阶段并不总是有 明确的病因。因此，疾病改进战略面临着各种慢性病的混合。 可能起源于许多cbhnplex的过程。Roo阶段的目标是 应用K99/R00研究大鼠体内分解代谢和促炎介质的局部调节 TMJ与疼痛相关行为和TMJ的发展 功能障碍。这项工作代表了K99/R00奖项向独立Roo阶段的过渡。在.期间 K99训练期间，PI调查了与膝关节炎相关的疾病因素和 为大鼠临床前模型开发了膝关节功能障碍的新的定量步态测量方法。在Roo中 阶段，提出了一种类似的方法来研究退行性疾病！TMJ的病理学。首先，我们将 开发新的方法来评估与大鼠TMJ疼痛和功能障碍相关的行为，包括 评估咀嚼运动学、饮食习惯、咬合力、睡眠和梳理行为的新系统 以及对口腔的敏感。同时，我们将开发一种慢性TMJ退行性变的模型 关节内注射一碘乙酸钠(MIA)；在此，将发生MIA诱导的TMJ退变 在几周的时间里，模拟慢性TMJ关节炎的级联，在这个模型中，我们将研究 血清、唾液和关节滑液中的TMJ病理分解代谢和促炎性标志物。 最后，我们将结合行为分析工具和我们的模型；TMJ退行性变来检查TLIE 疾病过程的局部调控与疾病后遗症发展的关系 与TMJ退行性变有关。通过这项工作，我们的目标是确定关键特征、阶段和； TMJ退行性变的介导者，目标是发展未来的介入研究。