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: 10399713
• 负责人: Michelle Lee Delco
• 金额: $ 1.4万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10399713
• 关键词: American; Ankle; Area; Arthritis; Biological; Biology; Biomedical Engineering; Cartilage; Cartilage injury; Clinical; Collaborations; Degenerative polyarthritis; Disease Progression; Doctor of Philosophy; Environment; Equus caballus; Functional disorder; Goals; Injury; Interdisciplinary Study; Knowledge; Laboratories; Learning; Link; Mechanics; Mentors; Minor; Mitochondria; Musculoskeletal; Orthopedics; Palliative Care; Pharmaceutical Preparations; Phase; Phase Transition; Professional Competence; Records; Regenerative Medicine; Research; Research Methodology; Research Personnel; Research Training; Role; Scientist; Specialty Boards; Surgeon; Testing; Time; Tissue Engineering; Training; Training Programs; Universities; Work; arthritic pain; career; cartilage repair; chronic pain; clinical practice; college; disability; graduate student; in vivo Model; insight; joint injury; mitochondrial dysfunction; prevent; skills; student mentoring; translational medicine

Project Summary/Abstract 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 applicant 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.

项目概要/摘要 此申请寻求专业委员会认证（美国兽医学院）的支持 马兽医完成从临床实践到转化性关节炎职业的转变 研究员。申请人将在康奈尔大学工作，师从Lisa A. Fortier博士（博士生导师， 导师）和 Larry Bonassar 博士（副博士生导师）。 Fortier 博士是一位临床医生兼科学家，也是一名马科骨科医生 外科医生，骨关节炎研究、软骨修复和再生医学领域的专家。博士。 拉里·博纳萨尔 (Larry Bonassar) 是一名生物医学工程师，是肌肉骨骼组织工程和 软骨的力学分析。 Fortier 和 Bonassar 之间的良好合作 实验室是康奈尔大学软骨小组的核心，是一个跨学科研究、培训和指导的机构 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 同事。 该提案分为两个阶段：指导阶段和过渡到独立阶段。期间 第一阶段，申请人将对基础软骨生物学、线粒体生物学和 骨关节炎，并完成博士学位。申请人和她的导师组建了一个跨学科的团队 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所需的重要概念和研究方法 完成拟议的研究，并了解其结果的生物学意义。他们也是 致力于指导候选人完成第二阶段，即向研究独立的过渡。 在第二阶段（向独立过渡），申请人将应用在过程中获得的知识、技能和见解 第一阶段研究早期踝关节创伤后体内模型中撞击引起的线粒体功能障碍 骨关节炎（PTOA）是在 Fortier 实验室开发的。我们预计这些研究将进一步推动基础研究 了解线粒体功能障碍在早期 PTOA 中的作用，将为临床提供证据。 使用线粒体稳定药物来阻止 PTOA 进展。申请人将完成严格的培训 假设驱动的研究计划，并获得必要的科学和超越替补的职业技能 在软骨线粒体病理学领域建立转化医学的职业生涯。

项目成果

Synovial fluid mitochondrial DNA concentration reflects the degree of cartilage damage after naturally occurring articular injury.

滑液线粒体DNA浓度反映了自然发生的关节损伤后软骨损伤的程度。

• DOI: 10.1016/j.joca.2023.03.013
• 发表时间: 2023
• 期刊: Osteoarthritis and cartilage
• 影响因子: 7
• 作者: Seewald,LA;Sabino,IG;Montney,KL;Delco,ML
• 通讯作者: Delco,ML

High-Plex RNA Expression Profiling of Formalin-Fixed Paraffin-Embedded Synovial Membrane Indicates Potential Mechanism of Mesenchymal Stromal Cells in the Mitigation of Posttraumatic Osteoarthritis.

福尔马林固定石蜡包埋滑膜的高倍 RNA 表达谱表明间充质基质细胞减轻创伤后骨关节炎的潜在机制。

• DOI: 10.1177/1947603521993521
• 发表时间: 2021
• 期刊: Cartilage
• 影响因子: 2.8
• 作者: Keller,LauraE;Fortier,LisaA;Delco,MichelleL;Okudaira,Mana;Becktell,Liliya;Cercone,Marta
• 通讯作者: Cercone,Marta

Human mesenchymal stromal cells release functional mitochondria in extracellular vesicles.

• DOI: 10.3389/fbioe.2022.870193
• 发表时间: 2022
• 期刊: FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
• 影响因子: 5.7
• 作者: Thomas, Matthew A.;Fahey, Megan J.;Pugliese, Brenna R.;Irwin, Rebecca M.;Antonyak, Marc A.;Delco, Michelle L.
• 通讯作者: Delco, Michelle L.

Intra-articular anaesthesia of the equine stifle improves foot lameness.

马膝关节的关节内麻醉可改善足部跛行。

• DOI: 10.1111/evj.13135
• 发表时间: 2020
• 期刊: Equine veterinary journal
• 影响因子: 2.2
• 作者: Radtke,A;Fortier,LA;Regan,S;Kraus,S;Delco,ML
• 通讯作者: Delco,ML

Mesenchymal stromal cells donate mitochondria to articular chondrocytes exposed to mitochondrial, environmental, and mechanical stress.

• DOI: 10.1038/s41598-022-25844-5
• 发表时间: 2022-12-13
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Fahey, Megan;Bennett, Maureen;Thomas, Matthew;Montney, Kaylee;Vivancos-Koopman, Irene;Pugliese, Brenna;Browning, Lindsay;Bonassar, Lawrence J.;Delco, Michelle
• 通讯作者: Delco, Michelle