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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要/摘要该申请寻求支持专业委员会认证的支持（美国兽医学院）马兽医为转化关节炎完成从临床实践到职业的过渡研究员。申请人将在康奈尔大学（Cornell University）在丽莎·A·福特尔（Lisa A. 导师）和Larry Bonassar博士（次要博士顾问）。临床科学家Fortier博士是马骨科外科医生和骨关节炎研究，软骨修复和再生医学领域的专家。博士生物医学工程师Larry Bonassar是肌肉骨骼组织工程和软骨的机械分析。堡垒和波纳萨尔之间建立了良好的合作实验室是康奈尔软骨小组的核心，这是一项跨学科研究，培训和心理化的环境。两者都有培训研究生的出色记录和心理博士后同事。该建议分为两个阶段，一个指导阶段，一个过渡到独立阶段。期间第一阶段，申请人将对基本软骨生物学，线粒体生物学和骨关节炎，并完成博士学位。申请人和她的精神汇集了一个跨学科合作者团队在此阶段为申请人的研究培训提供建议，指导和援助。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。他们也是致力于通过第二阶段的候选人为研究独立性的过渡。在第二阶段（过渡到独立性）中，申请人将应用知识，技能和见解第一阶段研究撞击引起的线粒体功能障碍在创伤后早期踝关节模型中骨关节炎（PTOA）在更稳定的实验室中发展。我们希望这些研究将进一步发展了解线粒体功能障碍在早期PTOA中的作用，并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的计划推动研究并获得必要的科学和超越的职业技能在软骨线粒体病理生物学领域建立转化医学的职业。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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