Chondrocyte viability is lost during high-rate impact loading by transfer of amplified strain, but not stress, to pericellular and cellular regions
Chondrocyte viability is lost during high-rate impact loading by transfer of amplified strain, but not stress, to pericellular and cellular regions
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DOI：
10.1016/j.joca.2019.07.018
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发表时间：
2019-12-01
影响因子：
7
通讯作者：
Neu, C. P.
中科院分区：
文献类型：
--
作者：
Argote, P. F.;Kaplan, J. T.;Neu, C. P.
目的：对软骨的破坏性冲击载荷引发创伤后骨关节炎（OA）。虽然细胞因子和酶水平调节疾病进展，但阐明细胞OA起源的特定机械线索值得进一步研究。我们定义了占主导地位的pericellular和细胞的应变/应力传递机制与cell death.Method：使用体外模型，我们研究了率依赖性负荷和空间定位的细胞活力在急性压痕和时间过程的研究。原子力显微镜（AFM）和磁共振成像（MRI）证实了软骨微观/宏观力学和结构后压痕的深度方向的变化。为了了解转移负载软骨域，我们计算模拟全场应变和应力措施间质基质，pericellular和cellular regions.Results：软骨细胞活力下降后快速的影响（80%/s）与缓慢加载（0.1%/s）或卸载控制。在压头-组织接触附近区域内的冲击过程中，活力立即丧失，但在组织培养7天后没有变化。AFM研究表明，80%/s的负载后刚度的损失，和MRI研究证实了增加的拉伸和剪切应变，但不是松弛。软骨细胞活力的基于图像的模式密切匹配的放大的最大主应变和剪切应变在间质基质，pericellular和cellular regions.Conclusion：快速压痕的软骨细胞死亡和降解软骨基质硬度压痕区域的计算估计。高应变率下的细胞死亡可能是由升高的拉伸应变驱动的，而不是基质应力。细胞周围基质和细胞中超过临界阈值的应变放大可能定义了创伤后OA早期损伤的起源点。由Elsevier Ltd代表国际骨关节炎研究协会出版。
Objective: Deleterious impact loading to cartilage initiates post-traumatic osteoarthritis (OA). While cytokine and enzyme levels regulate disease progression, specific mechanical cues that elucidate cellular OA origins merit further investigation. We defined the dominant pericellular and cellular strain/stress transfer mechanisms following bulk-tissue injury associated with cell death.Method: Using an in vitro model, we investigated rate-dependent loading and spatial localization of cell viability in acute indentation and time-course studies. Atomic force microscopy (AFM) and magnetic resonance imaging (MRI) confirmed depth-wise changes in cartilage micro-/macro-mechanics and structure post-indentation. To understand the transfer of loading to cartilage domains, we computationally modeled full-field strain and stress measures in interstitial matrix, pericellular and cellular regions.Results: Chondrocyte viability decreased following rapid impact (80%/s) vs slow loading (0.1%/s) or unloaded controls. Viability was lost immediately during impact within regions near the indenter-tissue contact but did not change over 7 days of tissue culture. AFM studies revealed a loss of stiffness following 80%/s loading, and MRI studies confirmed an increased tensile and shear strain, but not relaxometry. Image-based patterns of chondrocyte viability closely matched computational estimates of amplified maximum principal and shear strain in interstitial matrix, pericellular and cellular regions.Conclusion: Rapid indentation worsens chondrocyte death and degrades cartilage matrix stiffness in indentation regions. Cell death at high strain rates may be driven by elevated tensile strains, but not matrix stress. Strain amplification beyond critical thresholds in the pericellular matrix and cells may define a point of origin for early damage in post-traumatic OA. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.