Abstract：
Current experimental approaches cannot elucidate the effect of maladaptive changes on the main cartilage constituents during the degeneration process in osteoarthritis (OA). In silico approaches, however, allow creating \'virtual knock-out\' cases to elucidate these effects in a constituent-specific manner. We used such an approach to study the main mechanisms of cartilage degeneration in different mechanical loadings associated with the following OA etiologies: (1) physiological loading of degenerated cartilage, (2) injurious loading of healthy intact cartilage and (3) physiological loading of cartilage with a focal defect.
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.
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.
摘要：
目的：目前的实验方法无法阐明骨关节炎（OA）变性过程中适应不良变化对主要软骨成分的影响。在硅方法中，然而,允许创建“虚拟敲除”案例，以特定于成分的方式阐明这些影响。我们使用这种方法来研究与以下OA病因相关的不同机械负荷下软骨退化的主要机制：（i）退化软骨的生理负荷，(ii)健康完整软骨的损伤负荷和(iii)具有局灶性缺损的软骨的生理负荷。
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。
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。
