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: 7707704
• 负责人: Kyle D Allen
• 金额: $ 8.05万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-14 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7707704
• 关键词: Address; Adult; Affect; Animal Model; Animals; Area; Arthritis; Behavior; Bite Force; Cartilage; Cells; Clinical Treatment; Clinical assessments; Custom; Degenerative polyarthritis; Dermal; Development; Diet Habits; Disease; Drug Delivery Systems; Eating; Economic Burden; Faculty; Fibroblasts; Fibrocartilages; Gait; Genes; Goals; Human; Hypersensitivity; Inflammation; Inflammation Mediators; Inflammatory; Institution; Interleukin-1; Interleukin-1 Receptors; Interleukin-13; Interleukins; Intra-Articular Injections; Joints; Knee; Knee joint; Knowledge; Limb structure; Mandible; Measures; Mechanics; Mentors; Mentorship; Methods; Metric; Modeling; Musculoskeletal Diseases; Outcome; Pain; Pathology; Patients; Pattern; Pharmaceutical Preparations; Phase; Phenotype; Play; Population; Positioning Attribute; Postdoctoral Fellow; Pre-Clinical Model; Principal Investigator; Rattus; Research; Rheumatoid Arthritis; Rodent; Rodent Model; Role; Safety; Severities; Sleep; Staging; Stimulus; Symptoms; Synovial Membrane; System; Techniques; Technology; Temporomandibular Joint; Temporomandibular Joint Disorders; Temporomandibular joint arthritis; Temporomandibular joint osteoarthritis; Testing; Therapeutic; Therapeutic Intervention; Time; Training; Translating; Treatment Efficacy; Weight-Bearing state; Width; Withdrawal; anakinra; analog; arthropathies; career; design; design and construction; disability; drinking; economic impact; experience; foot; gait examination; innovation; instrumentation; interleukin-1 receptor type II; joint destruction; loss of function; meter; minimally invasive; novel; novel strategies; orofacial; overexpression; pre-clinical; programs; response; skills; soft tissue; tissue regeneration; tool; treatment strategy

DESCRIPTION (provided by applicant): Degenerative joint disorders, such as arthritis, affect a substantial percentage of the US population and have a significant economic burden. The focused use of disease modifying drugs and cellular Strategies for tissue regeneration offer great potential to treat these disorders; however, the safety and efficacy of these treatment strategies must first be evaluated in pre-clinical models. The purposes of this proposal, and the career aims of the principal investigator, are to create and refine techniques to evaluate joint function and symptoms in pre-clinical, animal models of arthritis and to investigate the potential for disease-modifying therapeutics to modify functional and symptomatic sequelae associated with arthritis. This proposal begins with the mentored phase where interleukin 1p (IL-lp) overexpression in the knee joint will be used as a rat model of unilateral inflammatory arthritis. The functional and symptomatic sequelae of this arthritis will be evaluated using custom-designed gait and pain sensitivity tests. Moreover, two ILIp antagonists, interleukin 1 receptor antagonist (111 Ra) and soluble interleukin 1 receptor type II (slHRII), will be evaluated for their ability to modify functional and symptomatic sequelae associated with knee arthritis. The PI will then transition skills and knowledge gained during the mentored phase to the study of temporomandibular joint (TMJ) disorders and their functional and symptomatic sequelae. In the independent stage, techniques and methods to assess the sequelae of TMJ disorders will be developed for rodent models, including systems to evaluate orofacial sensitivity, bite force, dietary habits, and sleep patterns. The intra-articular ILip over-expression model will then be adapted to initiate TMJ arthritis, and the developed technologies will be applied and assessed for their ability to modify the associated functional and symptomal sequelae. This proposal addresses the developments of novel treatment and assessment strategies for knee arthritis and TMJ disorders, drawing significantly on the PI's experience in TMJ research and the mentor institution's expertise in osteoarthritis and drug delivery. Moreover, this research plan will assist the PI in transitioning to a faculty position and establish an independent research program evaluating therapeutic interventions for TMJ disorders and degeneration.

描述（由申请人提供）：关节炎等退化性关节疾病会影响美国人口的很大一部分，并承受着巨大的经济负担。重点使用修饰药物的疾病和组织再生的细胞策略为治疗这些疾病提供了巨大的潜力。但是，这些治疗策略的安全性和功效必须首先在临床前模型中进行评估。该提案的目的以及首席研究者的职业目的是创建和完善技术，以评估临床前，关节炎动物模型的关节功能和症状，并研究疾病改良治疗剂的潜力，以修饰与关节炎相关的功能性和症状性sequelae。该建议始于指导阶段，膝关节中的白介素1p（IL-LP）过表达将用作单侧炎症性关节炎的大鼠模型。该关节炎的功能性和有症状后遗症将通过定制设计的步态和疼痛敏感性测试评估。此外，将评估两个ILIP拮抗剂，即白介素1受体拮抗剂（111 RA）和可溶性白介素1型II型受体（SLHRII），以评估其改变与膝关节炎相关的功能和症状后遗症的能力。然后，PI将在指导阶段获得过渡技巧和知识，以研究颞下颌关节（TMJ）疾病的研究及其功能性和有症状的后遗症。在独立阶段，将为啮齿动物模型开发评估TMJ疾病后遗症的技术和方法，包括评估口面敏感性，咬合力，饮食习惯和睡眠模式的系统。然后，关节内ILIP过表达模型将适应启动TMJ关节炎，并将应用和评估开发的技术修改相关功能和症状后遗症的能力。该建议旨在解决膝关节炎和TMJ疾病的新型治疗和评估策略的发展，这大大借鉴了PI在TMJ研究中的经验以及导师机构在骨关节炎和药物提供方面的专业知识。此外，该研究计划将有助于PI过渡到教师职位，并建立一个独立的研究计划，以评估TMJ疾病和退化的治疗干预措施。