Mitochondrial dysfunction as a link between cartilage injury and osteoarthritis

线粒体功能障碍是软骨损伤和骨关节炎之间的联系

• 批准号: 9275341
• 负责人: Michelle Lee Delco
• 金额: $ 14.7万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9275341
• 关键词: Acute; Alzheimer' s Disease; American; Anesthesia procedures; Animals; Ankle; Antioxidants; Apoptosis; Area; Arthritis; Attenuated; Basic Science; Biological; Biological Markers; Biology; Biomedical Engineering; Cartilage; Cartilage injury; Cell Death; Cell membrane; Cessation of life; Chondrocytes; Chronic; Clinical; Collaborations; Complex; Crista ampullaris; Data; Degenerative polyarthritis; Development; Diabetes Mellitus; Disease; Disease Progression; Doctor of Philosophy; Electron Microscopy; Engineering; Environment; Equus caballus; Evolution; Extracellular Matrix; Failure; Fluorescent Probes; Functional disorder; Glaucoma; Glycolysis; Goals; Harvest; Histology; Hour; Human; Image; In Situ; In Vitro; Injury; Interdisciplinary Study; Intervention; Knowledge; Laboratories; Learning; Lesion; Link; Magnetic Resonance Imaging; Measures; Mechanics; Mediating; Membrane Lipids; Membrane Potentials; Mentors; Microscope; Minor; Mitochondria; Modeling; Monitor; Morphology; Musculoskeletal; Orthopedic Surgery procedures; Orthopedics; Outcome Measure; Oxidative Phosphorylation; Oxygen Consumption; Pain; Pain Measurement; Palliative Care; Pathogenesis; Pathologic; Patients; Peptides; Pharmaceutical Preparations; Pharmacology; Phase; Phase Transition; Physiologic Intraocular Pressure; Porphyrins; Production; Professional Competence; Protons; Records; Regenerative Medicine; Research; Research Methodology; Research Personnel; Research Training; Respiration; Retinal Diseases; Role; Scientist; Secondary to; Serum; Specialty Boards; Stress; Stress Tests; Superoxide Dismutase; Surgeon; Syndrome; Synovial Fluid; Techniques; Technology; Testing; Therapeutic; Time; Tissue Engineering; Training; Training Programs; Translational Research; United States; Universities; Work; arthritic pain; articular cartilage; career; cartilage degradation; cartilage repair; chronic pain; clinical practice; college; disability; drug testing; effective therapy; experimental study; extracellular; fluorescence imaging; graduate student; in vivo; in vivo Model; indexing; injured; insight; intraoperative imaging; joint injury; mimetics; mitochondrial dysfunction; mitochondrial membrane; multidisciplinary; new technology; oxidative damage; prevent; public health relevance; respiratory; response; skills; student mentoring; translational medicine

 DESCRIPTION (provided by applicant): This application seeks support for a specialty board certified (American College of Veterinary Surgeons) equine veterinary surgeon to complete the transition from clinical practice to a career as a translational arthritis researcher. The applican will work at Cornell University under the guidance of Dr. Lisa A. Fortier (PhD advisor, Mentor) and Dr. Larry Bonassar (minor PhD advisor). Dr. Fortier, a clinician-scientist, is an equine orthopedic surgeon and an expert in the fields of osteoarthritis research, cartilage repair, and regenerative medicine. Dr. Larry Bonassar, a biomedical engineer, is an expert in the areas of musculoskeletal tissue engineering and mechanical analysis of cartilage. A well-established collaboration between the Fortier and Bonassar Laboratories is at the core of Cornell's Cartilage Group, an interdisciplinary research, training, and mentoring environment. Both have outstanding records for training graduate students and mentoring postdoctoral associates. This proposal is divided into two phases, a Mentored Phase, and a Transition-to-Independence Phase. During Phase I, the applicant will acquire a deeper understanding of basic cartilage biology, mitochondrial biology, and osteoarthritis, and complete a PhD degree. The applicant and her mentor have assembled an interdisciplinary team of collaborators to advise, mentor, and aid in the research training of the applicant during this phase. They are committed to helping the applicant learn important concepts and research methods needed to complete the proposed studies, and understand the biological significance of their results. They are also dedicated to mentoring the candidate through Phase II, the transition to research independence. In Phase II (Transition to Independence), the applicant will apply the knowledge, skills, and insights gained in Phase I to study impact-induced mitochondrial dysfunction in an vivo model of early ankle post-traumatic osteoarthritis (PTOA) developed in the Fortier laboratory. We expect these studies will further the fundamental understanding of the role of mitochondrial dysfunction in early PTOA, and will provide evidence for the clinical use of mitochondria stabilizing drugs to halt PTOA progression. The applicant will complete a rigorous training program in hypothesis driven research and gain the scientific and beyond-the-bench career skills necessary to establish a career in translational medicine with a niche in the area of cartilage mitochondrial pathobiology.

 描述（由申请人提供）：本申请寻求专业委员会认证（美国兽医学院）马兽医的支持，以完成从临床实践到翻译性关节炎研究人员职业生涯的过渡。申请人将在康奈尔大学工作，在丽莎博士的指导下。Fortier（博士生导师，导师）和Larry Bonassar博士（博士生导师）。Fortier博士是一位临床科学家，是一位马整形外科医生，也是骨关节炎研究，软骨修复和再生医学领域的专家。生物医学工程师Larry Bonassar博士是肌肉骨骼组织工程和软骨力学分析领域的专家。福捷实验室和博纳萨实验室之间建立良好的合作是康奈尔大学Carnell Group的核心，Carnell Group是一个跨学科的研究，培训和指导环境。两人在培养研究生和指导博士后方面都有出色的记录。该建议分为两个阶段，指导阶段和过渡到独立阶段。在第一阶段，申请人将获得基础软骨生物学，线粒体生物学和骨关节炎的更深入的了解，并完成博士学位。申请人和她的导师已经组建了一个跨学科的合作者团队，在此阶段为申请人的研究培训提供建议，指导和帮助。他们致力于帮助申请人学习完成拟议研究所需的重要概念和研究方法，并了解其结果的生物学意义。他们还致力于指导候选人通过第二阶段，过渡到研究独立。在第二阶段（过渡到独立）中，申请人将应用在第一阶段获得的知识，技能和见解，在Fortier实验室开发的早期踝关节创伤后骨关节炎（PTOA）体内模型中研究撞击诱导的线粒体功能障碍。我们希望这些研究将进一步从根本上了解线粒体功能障碍在PTOA早期的作用，并为临床使用线粒体稳定药物阻止PTOA进展提供证据。申请人将完成假设驱动研究的严格培训计划，并获得必要的科学和超越板凳的职业技能，以建立在软骨线粒体病理生物学领域的转化医学职业生涯。