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

骨关节炎（OA）是一种影响关节的慢性疾病，其中膝关节是最常见的关节之一。虽然过度的机械负荷，特别是在肥胖人群中，大大有助于其发病，OA现在被视为一种多因素疾病，其中低度慢性炎症具有核心作用。该项目将通过首次将（1）体重和体力活动作为机械负荷因素和（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相结合，为OA研究创建一个新的计算平台。其主要目的是开发一种空间和时间的多尺度计算方法，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。这种方法是一个新的出发点对建模的系统变化所造成的几个炎症相关factors.State的最先进的生物力学有限元（FE）模型将与非线性常微分方程（ODE）描述的亲和抗炎活动在膝关节。一组ODE将描述从周围脂肪组织中获得的促炎分子和抗炎分子随时间的浓度。通过巨噬细胞释放的酶的产生以及软骨和软骨下骨的过载，模拟软骨和软骨下骨随时间的降解。FE和ODE模型之间复杂的时间交互使得这项任务特别具有挑战性。整个建模平台将进行调整，以便在临床环境下测试OA发作和发展的预测能力。

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.