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

在退行性关节疾病中，关节的关节表面逐渐被破坏， 导致疼痛和关节功能障碍。大多数退行性关节疾病是慢性病变： 由多年来发生的疾病过程驱动，而终末期疾病可以描述为 软骨损失，软骨下骨重塑，功能障碍和疼痛，起始阶段并不总是有 明确的病因因此，疾病修饰策略面临着多种慢性疾病的混合， 这些过程可能是从许多复杂的起源中产生的。这一过程的ROO阶段的目标 K99/R 00应用是为了研究大鼠中分解代谢和促炎介质的局部调节 颞下颌关节（TMJ）和疼痛相关行为和TMJ的后续发展 功能障碍这项工作代表了K99/R 00奖项向独立ROO阶段的过渡。期间 K99培训，PI调查了与膝关节炎相关的疾病因素的局部调节， 为大鼠临床前模型开发了膝关节功能障碍的新定量步态测量。在ROO 阶段，提出了一个类似的方法用于研究退化！颞下颌关节的病理学一是 开发新的方法来评估与大鼠TMJ疼痛和功能障碍相关的因子，包括 评估咀嚼运动、饮食习惯、咬合力、睡眠和梳理行为的新系统 和面部敏感性。同时，我们将建立一个慢性TMJ变性模型， 关节内注射单碘乙酸钠（MIA）;在这里，由MIA诱导的TMJ变性将发生 在这个模型中，模拟TMJ关节炎的慢性级联，我们将研究 血清、唾液和TMJ滑液中TMJ病理的分解代谢和促炎标志物。 最后，我们将联合收割机行为分析工具与我们的TMJ退化模型相结合， 疾病过程的局部调节与疾病后遗症的发展之间的关系 与颞下颌关节退化有关通过这项工作，我们的目标是确定关键特征，阶段和; TMJ degeheration的介质，目的是发展未来的干预研究。

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.