Thymosin Beta 4: A Novel Biologic Therapy for Post-traumatic Osteoarthritis

胸腺素 Beta 4：一种治疗创伤后骨关节炎的新型生物疗法

• 批准号: 8784910
• 负责人: Ann Duskin Chauffe
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8784910
• 关键词: Acute; Analgesics; Analysis of Variance; Animals; Apoptosis; Arthritis; Behavior; Biological Response Modifier Therapy; Blinded; Cartilage; Cartilage injury; Chondrocytes; Cicatrix; Clinical Trials; Controlled Study; Cornea; Data; Degenerative polyarthritis; Development; Disease; Dose; Ensure; Evaluation; Fibrosis; Goals; Healed; Health; Health system; Heart; Human; Hypertrophy; Inflammation; Injury; Intervention; Intra-Articular Injections; Investigational New Drug Application; Joints; Journals; Knee; Knee Osteoarthritis; Laser Scanning Confocal Microscopy; Lead; Measures; Mechanics; Medial meniscus structure; Microbubbles; Modality; Modeling; Mus; Myocardial Infarction; Nature; Operative Surgical Procedures; Orthotic Devices; Pain; Pharmaceutical Preparations; Postoperative Period; Process; Property; Proteins; Rattus; Recurrence; Rehabilitation therapy; Replacement Arthroplasty; Research Personnel; Rodent Model; Sclerosis; Skin; Statistical Data Interpretation; Surface; Surgical Models; Tactile; Techniques; Technology; Testing; Thymosin; Tissues; Training; Translating; Trauma; Ultrasonography; United States Food and Drug Administration; Veterans; Work; Wound Healing; allodynia; arm; bone; cardiac repair; disability; efficacy evaluation; experience; functional outcomes; gait examination; healing; human disease; improved; improved functioning; joint destruction; joint injury; joint loading; joint stress; mouse model; neurotensin mimic 2; novel; prevent; public health relevance; response; thymosin beta(4); tissue repair; translational study

DESCRIPTION The overall objective of the study is to improve the long-term functional outcomes of Veterans suffering from osteoarthritis (OA) with the use of thymosin ¿4 (tb4). Tb4 is a protein found to extracellulary inhibit inflammation and promote tissue repair, as demonstrated in multiple animal studies and several investigational studies in humans. The proposal consists of two specific aims, each using a different mouse model of OA to test the hypothesis that tb4 will prevent the development of post-traumatic OA by preventing cartilage degeneration, chondrocyte hypertrophy and apoptosis, subchondral bone sclerosis, and synovial fibrosis. In the first model, surgical destabilization of the knee is used to induce OA. The second model is a non-invasive and utilizes mechanical joint loading. The force utilized does not lead to joint damage when it occurs individually. However, when the force is sustained leads to OA-type changes. These models mimic the post-traumatic OA Veterans develop either after sustaining trauma or after repeated joint stress. In the surgical destabilization of the medial meniscus arm of the study (Specific Aim 1), tb4 will be injected under ultrasound guidance at weekly intervals for 16 weeks, thereby mimicking acute injury and the rehabilitation process. The joint loading arm (Specific Aim 2) mimics the OA that results from recurrent joint stress. Similarly, tb4 will be injected unde ultrasound guidance into the right knee at weekly intervals for 8 weeks. In both arms of the study, control mice will receive PBS. Evaluation of the efficacy of tb4 will be multifaceted with histopathologic scoring, laser scanning confocal microscopy and microbubble ultrasound assessment. Additionally, evaluation of murine functional behaviors will be used to assess the symptomatic consequences of OA and impact of tb4 treatment with dynamic gait analysis and tactile allodynia response. Throughout the study, investigators will be blinded to treatment. Statistical analysis of the data will include the use repeated measures of ANOVA. In keeping with the goals of RR&D CDA-1, Dr. Chauffe will gain essential investigational experience. This will culminate with her ability to successfully work as an independent investigator with a focus on preventing disability due to arthritis. The training plan outlined in this proposal includes extensive educational components, both in the lab and didactic, ensuring this goal is achieved.

描述 总体目的是改善使用骨关节炎（OA）的长期结局，并使用缠绵的使用膜蛋白。 4（TB4）是一种蛋白通过侵蚀性，在第一型模型中，膝盖纤维化是膝盖的，膝盖的手术是诱导OA的。它会单独发生。在每周的时间间隔16周，在每周的关节压力中模仿了Anjry Anjry和Rehabilitatient的过程对照小鼠的武器将对TB4的疗效，并在整个研究中使用动态性同差响应遵循RR＆D CDA-1的目标，Chauffe博士将获得Essentigatigation的实验。 ，确保实现这一目标。