Inflammation and mechanical loading in osteoarthritis- an integrative multi-scale approach

骨关节炎的炎症和机械负荷——一种综合的多尺度方法

• 批准号: 2747654
• 金额: --
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2747654
• 关键词: Inflammation; mechanical; loading; osteoarthritis; integrative

Osteoarthritis (OA) is a chronic disease affecting the joints, with the knee being one of the joints most commonly affected. Although excessive mechanical loading, in particular in obese people, contributes greatly to its onset, OA is now seen as a multifactorial disorder in which low-grade, chronic inflammation has a central role. This project will create a novel computational platform for the study of OA by combining for the first time (1) weight and physical activity as mechanical loading factors and (2) obesity and nutritional factors with the release of cytokines and adipocytes from the surrounding adipose tissue of the joint. The main aim is to develop a spatial and temporal multiscale computational approach that describes the interactions between the molecular pathways related to joint inflammation and the daily physical loading that contributes to cartilage and bone damage within the joint. This approach is a new departure towards the modelling of systemic changes resulting from several inflammation-related factors.State-of-the-art biomechanical finite element (FE) models will be coupled with non-linear ordinary differential equations (ODE) describing the pro- and anti-inflammatory activities within the knee joint. A set of ODEs will describe the concentration over time of pro- and anti-inflammatory molecules available from the surrounding adipose tissue. The simulation of cartilage and subchondral bone degradation over time through the production of enzymes released by macrophages and overloading of the cartilage and subchondral bone will be modelled. The complex time interaction between the FE and the ODE model makes this task particularly challenging. The overall modelling platform will be adapted to enable testing the predictive capability of OA onset and development under clinical setting.

骨关节炎(OA)是一种影响关节的慢性疾病，膝关节是最常见的关节之一。虽然过度的机械负荷，特别是在肥胖者中，极大地促进了其发病，但现在人们认为OA是一种多因素疾病，在其中低级别的慢性炎症起着核心作用。该项目将首次将(1)体重和体力活动作为机械负荷因素，(2)肥胖和营养因素与关节周围脂肪组织释放的细胞因子和脂肪细胞结合起来，为骨性关节炎的研究创造一个新的计算平台。主要目的是开发一种时空多尺度计算方法，描述与关节炎症相关的分子途径与导致关节内软骨和骨损伤的日常物理负荷之间的相互作用。这种方法是对由多种炎症相关因素引起的系统变化建模的新的突破。最新的生物力学有限元(FE)模型将与描述膝关节内促炎和抗炎活动的非线性常微分方程组(ODE)相耦合。一组ODES将描述随着时间的推移，周围脂肪组织中可用的促炎和抗炎分子的浓度。将模拟软骨和软骨下骨随时间的降解，通过产生巨噬细胞释放的酶和软骨和软骨下骨的过载。有限元和常微分方程模型之间复杂的时间相互作用使这项任务特别具有挑战性。将对整体建模平台进行调整，以测试临床环境下对骨性关节炎发病和发展的预测能力。