Biomechanical and Biological Predictors of Cartilage Health Following Meniscus Injury

摘要 半月板损伤常与早发性骨关节炎（OA）相关。部分直肠切除术， 去除受损的尿道组织是最常进行的整形外科手术。虽然这 手术可以在短期内缓解症状，近35%的患者出现放射学证据 术后5-7年内发生OA。然而，这种早发性OA的原因尚不清楚。一个潜在 椎间盘切除术后膝关节OA进展的途径是通过改变关节 软骨然而，其他研究表明，生物因素，如关节炎症可能发挥作用， 重要的作用最近，通过结合MR成像、3D建模和双平面X线摄影， 研究小组已经表明，内侧踝关节损伤改变了内侧踝关节和外侧踝关节的软骨-软骨接触应变， 和侧隔室。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，其是可以指示关节炎的生物标志物。 降解总之，这些结果表明，生物力学和生物学因素发挥了重要作用， 踝关节损伤后OA的发展。然而，部分椎间盘切除术对这些变化的作用是 不清楚因此，对关节前的生物力学和生物环境进行综合评价， 以及部分椎间盘切除术后，将阐明导致早发性OA的因素。我们的整体 假设在部分椎间盘切除后， 关节将预示软骨退化。此外，当生物力学和生物学预测因子 结合患者人口统计学和临床特征，我们将确定明确的 软骨退化高危患者的临床表型。 将通过基于MR的软骨厚度测量评估软骨变性， 混合物.使用高速双平面X线和MR成像，在体内软骨应变在两个膝盖的病人， 将测量单侧内侧半月板损伤患者在手术前和手术后对跑步机行走的反应。 手术还将收集滑液和血清，以及一组促炎介质和组织 将测量代谢生物标志物。将通过流式细胞术进行滑液免疫细胞分析。 利用这些生物力学和生物学因素，我们将确定参与者在软骨风险增加 手术后两年发生退化。然后，使用结合生物力学因素的预测模型， 生物学因素，人口统计学和临床特征，我们将开发明确的临床表型， 软骨退化风险。重要的是，这些表型的发展将实现靶向治疗 方法侧重于手术、药物靶点和非药物干预，如 物理康复策略或减肥，以防止软骨退化。

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.