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: 10230722
• 负责人: Louis E. DeFrate
• 金额: $ 69.65万
• 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/10230722
• 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; Diagnostic radiologic examination; Dinoprostone; Environment; Evaluation; 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; articular cartilage; base; 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; 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.

摘要 半月板损伤常与早发性骨关节炎(OA)有关。半月板部分切除术 切除受损的半月板组织是最常见的骨科手术。虽然这件事 手术可以在短期内缓解症状，近35%的患者出现放射学证据 在手术后5-7年内发生骨性关节炎。然而，这种早发性骨性关节炎的原因尚不清楚。一种潜力 半月板切除后膝关节骨性关节炎进展的途径是通过改变关节负荷 软骨。然而，其他研究表明，生物因素，如关节炎症，可能在 重要的角色。最近，通过结合磁共振成像、3D建模和双平面放射成像，我们的 研究小组已经证明，内侧半月板损伤改变了内侧半月板和内侧半月板软骨之间的接触应变 和侧舱。此外，我们发现，增加的压力与增加的 滑液中基质金属蛋白酶的活性，一个可能指示关节的生物标志物 退化。综上所述，这些结果表明生物力学和生物因素在 半月板损伤后骨性关节炎的发展。然而，半月板部分切除术对这些变化的作用是 不清楚。从而对关节前的生物力学和生物环境进行综合评价。 半月板部分切除后将阐明导致早发性骨性关节炎的因素。我们的整体 假说是半月板部分切除后，半月板的生物力学和生物学变化 关节会预测软骨退变。此外，当生物力学和生物学预测指标 结合患者的人口统计和临床特征，我们将确定明确的 软骨退变高危患者的临床表型。 软骨退行性变将通过基于MR的软骨厚度和 组成。应用高速双平面x线和磁共振成像技术，活体观察患者双膝软骨的应变情况 对于单侧内侧半月板损伤，将在手术前和手术后通过跑步机行走进行测量。 做手术。还将收集滑液和血清，以及一组促炎介质和组织 代谢生物标记物将被测量。滑液免疫细胞分析将通过流式细胞仪进行。 利用这些生物力学和生物因素，我们将确定软骨风险增加的参与者。 术后两年出现退行性变。然后，使用结合生物力学因素的预测模型， 生物学因素、人口学和临床特征，我们将制定明确的临床表型 软骨退变的风险。重要的是，这些表型的发展将使靶向治疗成为可能。 侧重于手术、药物靶点和非药物干预的方法，如 身体康复策略或减肥，防止软骨退变。