模拟创伤后骨关节炎中机械炎症与细胞因子驱动炎症所致软骨退变的计算框架
A computational framework to model cartilage degeneration induced by mechanoinflammation and cytokine-driven inflammation in post-traumatic osteoarthritis
一个机械生物学有限元框架可模拟创伤后骨关节炎（PTOA）中由损伤载荷引发的机械炎症和细胞因子驱动炎症所触发的细胞介导蛋白水解性软骨降解。该模型复现了实验观察到的胶原与聚集蛋白聚糖随深度变化的丢失：机械炎症诱导短暂响应，而细胞因子驱动炎症维持长期基质降解。敏感性分析显示，机械炎症驱动的降解主要受每细胞蛋白酶产量控制，细胞因子驱动的降解则对细胞刺激速率更敏感。该框架为研究蛋白水解性软骨退变提供机制基础，并支持未来对减轻 PTOA 软骨降解治疗策略的计算评估。
来源：PLOS Computational Biology · journals.plos.org
by Moustafa Hamada, Atte S. A. Eskelinen, Joonas P. Kosonen, Sanna Hakonen, Cristina Florea, Alan J. Grodzinsky, Rami K. Korhonen, Petri Tanska
Knee joint injury is a major risk factor for post-traumatic osteoarthritis (PTOA), often associated with early cartilage degeneration. Mechanical overloading and cytokine-driven inflammation are key drivers of this process, yet the underlying mechanisms and their distinct temporal and spatial contributions to cartilage degradation remain unclear. Here, we present a mechanobiological finite element framework that simulates cartilage degradation through cell-mediated proteolytic activity triggered by injurious loading-driven mechanoinflammation and cytokine-driven inflammation. The model reproduces experimentally observed depth-dependent loss of collagen and aggrecan, with mechanoinflammation inducing a transient response and cytokine-driven inflammation sustaining prolonged matrix degradation. Sensitivity analysis further shows that mechanoinflammation-driven degradation is governed mainly by protease production per cell, whereas cytokine-driven degradation is more sensitive to the rate of cellular stimulation. Together, this framework provides a mechanistic basis to study proteolytic cartilage degeneration and supports future in silico evaluation of therapeutic strategies aimed at mitigating cartilage degradation in PTOA.