Modeling Cartilage Degeneration by Combining Systems Biology and Biomechanical Approaches

在发达国家，每六个人中就有一个受到关节炎的影响。骨性关节炎是最常见的关节炎类型，其特征是软骨退变导致剧烈疼痛，关节活动受限，整体生活质量下降。目前，这种疾病的治疗方法是止痛药，只需推迟关节置换，不会影响软骨退化。这个项目的目标是了解软骨退化并提供经过验证的体外有效的化合物。为了完成这项任务，我们遵循了涉及系统生物学和生物力学的多学科和整体方法。系统生物学将被应用于分析疾病并在细胞水平上发现药物治疗机会。高通量蛋白质组测量和细胞信号网络以及机器学习算法将被用来完成这项任务。然后，将使用软骨退化实时监测设备对已确定的治疗疾病的化合物进行体外测试，并使用实验和计算生物力学的工具进行定量评估。因此，存在着从细胞水平到组织水平的转变。总之，将在细胞内和细胞外机制与关节软骨的力学行为之间建立联系。本研究项目的研究跨越了不同的规模，为骨关节炎的研究提供了新的和创新的见解，并为一种具有高度医学、经济和社会影响的疾病的治疗产生了结果。

One of every six people is affected by arthritis in the developed countries. Osteoarthritis, the most common type of arthritis, is characterized by cartilage degeneration leading to severe pain, restriction of joint motion and reduction of the overall quality of life. Currently, this disease is treated with pain-relief drugs that simply delay joint replacement and do not affect cartilage degeneration. The goal of this project is to understand cartilage degeneration and deliver compounds with proven in vitro efficacy.To accomplish this task, we follow a multidisciplinary and holistic approach involving systems biology and biomechanics. Systems biology will be applied to analyze the disease and discover drug treatment opportunities on the cellular level. High-throughput proteomic measurements and cell signaling networks in combination with machine-learning algorithms will be used to accomplish this task. The identified compounds for disease treatment will then be tested in vitro with a real time monitoring device of cartilage degeneration and quantitatively evaluated with tools from experimental and computational biomechanics. Thus, there is a shift from the cellular level to the tissue level. Altogether a connection between intra -and extracellular mechanisms and the mechanical behavior of articular cartilage will be made.The studies in this research project are spanned over different scales, providing new and innovative insights in osteoarthritis research and generating results for the treatment of a disease with high medical, economic and social impact.