Role of the Infrapatellar Fat Pad in the Development of Post-Traumatic Osteoarthritis Following Blunt Impact to the Knee Joint

髌下脂肪垫在膝关节钝性撞击后发生创伤后骨关节炎中的作用

• 批准号: 10654180
• 负责人: John Leicester Williams
• 金额: $ 42.53万
• 依托单位: UNIVERSITY OF MEMPHIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10654180
• 关键词: Accounting; Acute; Adipose tissue; Affect; American; Animal Model; Animals; Anterior; Appearance; Athletic Injuries; Behavior; Biochemical Pathway; Biomechanics; Blunt Trauma; Cartilage; Case Study; Cells; Cephalic; Chondrocytes; Clinical; Connective Tissue; Control Animal; Contusions; Degenerative polyarthritis; Deterioration; Development; Disease; Drops; Drug or chemical Tissue Distribution; Edema; Engineering; Excision; Failure; Fatty acid glycerol esters; Female; Femur; Fracture; Geography; Glycosaminoglycans; Goals; Health; Histopathology; Homeostasis; Inflammation; Inflammatory; Injury; Interdisciplinary Study; Intervention; Joints; Knee; Knee bone; Knee joint; Laboratories; Lateral; Ligaments; Limb structure; Link; Lower Extremity; Medial; Mediator; Meniscus structure of joint; Microcomputers; Modeling; Molecular; Operative Surgical Procedures; Oryctolagus cuniculus; Pathogenesis; Pathologic; Pathology; Pathway interactions; Patients; Play; Productivity; Property; Proteomics; Qualifying; Reporting; Research; Role; Serum; Severities; Shapes; Sports; Structure; Synovial Fluid; Testing; Time; Tissues; Training; Trauma; Traumatic Arthropathy; Work; X-Ray Computed Tomography; articular cartilage; biomechanical test; bone; calcification; cartilage cell; comparative; guinea pig model; improved; injured; joint injury; male; metabolomics; motor vehicle injury; negative affect; pressure; prevent; subchondral bone; undergraduate student; Accounting; Acute; Adipose tissue; Affect; American; Animal Model; Animals; Anterior; Appearance; Athletic Injuries; Behavior; Biochemical Pathway; Biomechanics; Blunt Trauma; Cartilage; Case Study; Cells; Cephalic; Chondrocytes; Clinical; Connective Tissue; Control Animal; Contusions; Degenerative polyarthritis; Deterioration; Development; Disease; Drops; Drug or chemical Tissue Distribution; Edema; Engineering; Excision; Failure; Fatty acid glycerol esters; Female; Femur; Fracture; Geography; Glycosaminoglycans; Goals; Health; Histopathology; Homeostasis; Inflammation; Inflammatory; Injury; Interdisciplinary Study; Intervention; Joints; Knee; Knee bone; Knee joint; Laboratories; Lateral; Ligaments; Limb structure; Link; Lower Extremity; Medial; Mediator; Meniscus structure of joint; Microcomputers; Modeling; Molecular; Operative Surgical Procedures; Oryctolagus cuniculus; Pathogenesis; Pathologic; Pathology; Pathway interactions; Patients; Play; Productivity; Property; Proteomics; Qualifying; Reporting; Research; Role; Serum; Severities; Shapes; Sports; Structure; Synovial Fluid; Testing; Time; Tissues; Training; Trauma; Traumatic Arthropathy; Work; X-Ray Computed Tomography; articular cartilage; biomechanical test; bone; calcification; cartilage cell; comparative; guinea pig model; improved; injured; joint injury; male; metabolomics; motor vehicle injury; negative affect; pressure; prevent; subchondral bone; undergraduate student

PROJECT SUMMARY Excessive compressive load caused by blunt impact to the knee, such as during a car accident or sports injury, is known to lead to osteoarthritis (OA) within the joint. Often times, no gross ligament or meniscal damage is present in these cases; given this, occult damage is not treated, representing an underserved opportunity to prevent later pathology. Our laboratory previously developed a model, using the Flemish Giant rabbit, to study the effects of impact compressive loading to the knee. This model has shown that blunt impacts result in: (i) cartilage damage; (ii) microcracks at the interface between calcified cartilage and underlying subchondral bone in the tibial plateau; and (iii) significant loss of glycosaminoglycans in the meniscal tissue, all of which point to clinical signs of post-traumatic osteoarthritis (PTOA). Interestingly, recent studies by our group using the Hartley guinea pig model of spontaneous OA have shown that early removal of the infrapatellar fat pad (IFP) was able to prevent progression of pathology (i.e. histopathology and micro-computer tomography scores were reduced in the limbs with the IFP removed compared to sham control). Improvement in limbs was attributed to the development of a replacement fibrous connective tissue (FCT) in place of the IFP, which demonstrated less evidence of inflammation and fewer changes in material properties of joint tissues than the native adipose depot. Given this, the goal of the present study is to further elucidate the role of the IFP in PTOA development in our Flemish Giant rabbit model of compressive loading. We propose to determine the role that injured IFP plays in knee degeneration and identify whether biomechanical and/or molecular pathways may be influencing the development of PTOA post-injury. We hypothesize that removal of the IFP will prevent/decrease PTOA following blunt impact to the knee. We will accomplish this via two subaims: (1) Correlate the presence and severity of PTOA to the tissue distribution of inflammatory/pathologic mediators in the joint. Proposed work will quantitate the presence of key inflammatory and matrix degrading molecules in joint tissues, serum (systemic changes), and synovial fluid (local changes) via proteomics and metabolomics. (2) Assess the biomechanical properties of the bone, cartilage, and menisci following removal of the IFP. Biomechanical properties of joint tissue will be characterized using: cranial drawer tests; tensile tests, which will evaluate the time dependent and failure properties of the whole knee joint; macro-indentation testing of articular cartilage, menisci, IFP, and FCT, which will establish the comparative stiffness of these structures; and shear and compression testing of the IFP and FCT to determine material behavior. By pursuing this mechanistic rationale to explain the negative ramifications of the IFP on knee joint health, our work may support early removal of the IFP in patients who have suffered a blunt trauma to the knee joint. Our dual approach will be helmed by a uniquely qualified research team with demonstrated productivity. Additionally, this project will train undergraduates in multi-disciplinary research ranging from molecular mechanisms to engineering.

项目摘要 由于膝盖的钝性撞击引起的过多压缩负荷，例如在车祸或运动伤害期间， 已知会导致关节内骨关节炎（OA）。通常情况下，没有严重的韧带或半月板伤害是 在这些情况下存在；鉴于此，没有治疗神秘的伤害，代表了服务不足的机会 防止以后的病理。我们的实验室以前使用佛兰芒巨型兔子开发了一个模型来研究 冲击压缩负荷对膝盖的影响。该模型表明钝的影响导致：（i） 软骨伤害； （ii）在钙化软骨和下层下骨之间的接口处的微裂纹 在胫骨高原； （iii）半月板组织中糖胺聚糖的显着损失，所有这些指向 创伤后骨关节炎（PTOA）的临床体征。有趣的是，我们小组使用Hartley的最新研究 自发OA的豚鼠模型表明，及早去除infrapatellar脂肪垫（IFP）能够 为防止病理学进展（即组织病理学和微型计算机断层扫描评分降低 与假对照相比，在四肢中删除了IFP）。四肢的改善归因于 开发替换纤维结缔组织（FCT）代替IFP，这表明较少 与天然脂肪仓库相比，炎症的证据和关节组织材料特性的变化较少。 鉴于此，本研究的目的是进一步阐明IFP在PTOA开发中的作用 压缩载荷的佛兰德巨型兔子模型。我们建议确定IFP受伤的作用 膝盖变性并确定生物力学和/或分子途径是否可能影响 PTOA后伤害后的发展。我们假设去除IFP将阻止/减少PTOA 钝对膝盖的冲击。我们将通过两个subiaims实现这一目标：（1）将存在和 PTOA对关节中炎症/病理介质的组织分布的严重程度。拟议的工作将 定量关节组织中的关键炎症和基质降解分子的存在（全身性） 通过蛋白质组学和代谢组学变化）和滑液（局部变化）。 （2）评估生物力学 去除IFP后，骨骼，软骨和半月板的特性。关节的生物力学特性 组织将使用：颅抽屉测试来表征；拉伸测试，将评估依赖时间和 整个膝关节的失败特性；关节软骨的宏观调查测试，拟南期，IFP和FCT， 这将建立这些结构的比较刚度；以及IFP的剪切和压缩测试 和FCT确定材料行为。通过追求这种机械理由来解释负面 IFP对膝关节健康的影响，我们的工作可能支持早日删除IFP 膝盖关节遭受了钝的创伤。我们的双重方法将由一个独特的资格研究团队主持 具有证明的生产力。此外，该项目将在多学科研究中培训本科生 从分子机制到工程。