We used the recently developed Cartilage Adaptive REorientation Degeneration (CARED) framework to simulate cartilage degeneration associated with primary and secondary OA (OA cases (1)-(3)). CARED incorporates numerical description of tissue-level cartilage degeneration mechanisms in OA, namely, collagen degradation, collagen reorientation, fixed charged density loss and tissue hydration increase following mechanical loading. We created \'virtual knock-out\' scenarios by deactivating these degenerative processes one at a time in each of the three OA cases.
In the injurious loading of intact and physiological loading of degenerated cartilage, collagen degradation drives degenerative changes through fixed charge density loss and tissue hydration rise. In contrast, the two later mechanisms were more prominent in the focal defect cartilage model.
The virtual knock-out models reveal that injurious loading to intact cartilage and physiological loading to degenerated cartilage induce initial degenerative changes in the collagen network, whereas, in the presence of a focal cartilage defect, mechanical loading initially causes proteoglycans (PG) depletion, before changes in the collagen fibril network occur.
方法:我们使用最近开发的软骨自适应复位退变(CARED)框架来模拟与原发性和继发性OA相关的软骨退变(OA病例(i)-(iii))。CARED结合了OA中组织水平软骨退变机制的数值描述,即,胶原蛋白降解,胶原蛋白重新定向,固定电荷密度损失和组织水化增加后的机械负荷。我们通过在三个OA案例中的每个案例中一次一个地停用这些退化过程来创建“虚拟敲除”场景。
结果:在退化软骨的完整和生理负荷的有害负荷中,胶原蛋白降解通过固定电荷密度损失和组织水化上升驱动退行性变化。相比之下,后两种机制在局灶性缺损软骨模型中更为突出。
结论:虚拟敲除模型显示,完整软骨的损伤负荷和退化软骨的生理负荷可引起胶原网络的初始退行性变化,然而,在存在局灶性软骨缺损的情况下,机械加载最初会导致PG耗尽,在胶原蛋白原纤维网络发生变化之前。