Biomechanical and Biological Predictors of Cartilage Health Following Meniscus Injury

半月板损伤后软骨健康的生物力学和生物学预测因子

• 批准号: 10383708
• 负责人: Louis E. DeFrate
• 金额: $ 67.98万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-05 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10383708
• 关键词: Biochemical; Biological; Biological Factors; Biological Markers; Biomechanics; Body Weight decreased; Cadaver; Cartilage; Cells; Characteristics; Clinical; Cluster Analysis; Computer Models; Data; Degenerative polyarthritis; Development; Dinoprostone; Environment; Flow Cytometry; Future; Goals; Health; Image; Immune; Individual; Inflammation Mediators; Inflammatory; Intervention; Joints; Knee; Knee Osteoarthritis; Lateral; Lead; Machine Learning; Magnetic Resonance Imaging; Matrix Metalloproteinases; Measures; Medial; Medial meniscus structure; Meniscus structure of joint; Metabolic; Methods; Operative Surgical Procedures; Orthopedic Procedures; Participant; Pathway interactions; Patient-Focused Outcomes; Patients; Pharmacologic Substance; Phenotype; Physical Rehabilitation; Physical therapy; Play; Procedures; Public Health; Risk; Role; Serum; Speed; Subgroup; Suggestion; Synovial Fluid; Techniques; Thick; Time; Tissues; Validation; Walking; X-Ray Medical Imaging; articular cartilage; base; biomechanical test; care outcomes; cartilage degradation; clinical phenotype; demographics; disability; early onset; high risk; imaging biomarker; improved; improved outcome; in vivo; in vivo imaging; joint destruction; joint inflammation; joint injury; macrophage; meniscus injury; predictive modeling; prevent; primary outcome; radiological imaging; random forest; rehabilitation strategy; response; targeted treatment; three-dimensional modeling; treadmill

Abstract Injury of the meniscus is frequently associated with early onset osteoarthritis (OA). Partial meniscectomy to remove the damaged meniscal tissue is the most commonly performed orthopaedic procedure. While this procedure can provide symptomatic relief in the short term, nearly 35% of patients develop radiographic evidence of OA within 5-7 years following surgery. However, the causes for this early onset OA are unknown. One potential pathway for the progression of knee OA following meniscectomy is through altered loading of the articular cartilage. However, other studies suggest that biological factors, such as joint inflammation may play an important role. Recently, through a combination of MR imaging, 3D modeling, and biplanar radiography, our team has shown that medial meniscal injury alters the cartilage-to-cartilage contact strains in both the medial and lateral compartments. In addition, we found that increased strain was correlated with increased levels of matrix metalloproteinase (MMP) activity in the synovial fluid, a biomarker which may be indicative of joint degradation. Together, these results suggest that biomechanical and biological factors play an important role in the development of OA after meniscal injury. However, the role of partial meniscectomy on these changes is unclear. Thus, a comprehensive evaluation of the biomechanical and biological environment of the joint before and after partial meniscectomy will elucidate the factors that contribute to early onset OA. Our overall hypothesis is that following partial meniscectomy, both biomechanical and biological changes in the joint will predict cartilage degeneration. Furthermore, when biomechanical and biological predictors are combined together with patient demographics and clinical characteristics, we will identify well-defined clinical phenotypes of patients at high risk of cartilage degeneration. Cartilage degeneration will be assessed through MR-based measures of cartilage thickness and composition. Using high speed biplanar x-ray and MR imaging, in vivo cartilage strains in both knees of patients with unilateral medial meniscus injury will be measured in response to treadmill walking prior to surgery and after surgery. Synovial fluid and serum will also be collected and a panel of pro-inflammatory mediators and tissue metabolic biomarkers will be measured. Synovial fluid immune cell analyses will be performed by flow cytometry. Using these biomechanical and biological factors, we will identify participants at increased risk for cartilage degeneration at two years after surgery. Then, using predictive models combining biomechanical factors, biological factors, demographics, and clinical characteristics, we will develop well-defined clinical phenotypes of cartilage degeneration risk. Importantly, the development of these phenotypes will enable targeted treatment approaches focused on surgery, pharmaceutical targets, and non-pharmacological interventions, such as physical rehabilitation strategies or weight loss, to prevent cartilage degeneration.

抽象的 半月板的损伤经常与早期发作骨关节炎（OA）有关。部分半月板切除术 去除损坏的半月板组织是最常见的骨科手术。同时 手术可以在短期内提供症状缓解，近35％的患者产生了射线照相证据 手术后5 - 7年内的OA。但是，这种早期发作的原因是未知的。一个潜力 半月板切除术后膝盖OA进展的途径是通过改变关节的负载 软骨。但是，其他研究表明，诸如关节炎症之类的生物学因素可能会起作用 重要角色。最近，通过MR成像，3D建模和Biplanar射线照相的组合，我们 团队表明，内侧半月板损伤改变了两种内侧的软骨对 - 肉毒接触菌株 和侧室。此外，我们发现增加的应变与增加的水平相关 滑液中的基质金属蛋白酶（MMP）活性，一种生物标志物，可能表明关节 降解。这些结果共同表明，生物力学和生物学因素在 半月板受伤后OA的发展。但是，部分半月板切除术对这些变化的作用是 不清楚。因此，对关节之前的生物力学和生物学环境进行了全面评估 部分半月板切除术后将阐明导致早期OA的因素。我们的整体 假设是，在部分半月板切除术之后，无论是生物力学还是生物学变化 关节将预测软骨变性。此外，当生物力学和生物学预测因子是 与患者人口统计和临床特征结合在一起，我们将确定定义明确的 具有高软骨变性风险的患者的临床表型。 软骨变性将通过基于MR的软骨厚度和 作品。使用高速Biplanar X射线和MR成像，两种患者膝盖的体内软骨菌株 通过单方面的半月板损伤将在手术前和之后响应跑步机行走来测量 外科手术。也将收集滑液和血清，并进行一组促炎性介质和组织 将测量代谢生物标志物。滑液免疫细胞分析将通过流式细胞仪进行。 使用这些生物力学和生物学因素，我们将确定有软骨风险增加的参与者 手术两年后的变性。然后，使用结合生物力学因子的预测模型， 生物学因素，人口统计学和临床​​特征，我们将开发明确定义的临床表型 软骨变性风险。重要的是，这些表型的发展将实现目标治疗 专注于手术，药物靶标和非药理学干预措施的方法，例如 身体康复策略或体重减轻，以防止软骨变性。