Huang Wenjing, Warner Mia, Sasaki Hikaru, Furukawa Katsuko S, Ushida Takashi
Department of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
Department of Bioengineering, College of Engineering, Computing and Applied Sciences, Clemson University, 301 Rhodes Research Center, Clemson, SC, 29634-0905, USA.
J Mech Behav Biomed Mater. 2020 Dec;112:104088. doi: 10.1016/j.jmbbm.2020.104088. Epub 2020 Sep 15.
Exposure to excessive stress is associated with the pathogenesis of osteoarthritis, a joint disease involved in the degeneration of articular cartilage. Mechanical properties of mature articular cartilage are known to be depth zone-dependent. Although chondrocyte death was observed in articular cartilage after excessive stress loading in vitro, few studies have investigated the correlation between chondrocyte death and local mechanical strains in a depth dependent manner. Here, we developed a real-time observation system of cut cartilage samples under an excessive stress loading (18 MPa) at low (3.5%/s) and high (35%/s) strain rates on the microscope stage, which is regarded as injurious compression in vivo. Using this system, real-time monitoring of local deformations was conducted during compression, and local chondrocyte death was investigated after short-term culture. The results showed that the dead cells were mainly observed in the surface layer at a high strain rate. In contrast, the dead cells were relatively concentrated not in the surface layer but in the middle layer at a low strain rate. The local strain measurements showed that the dead cell distributions were correlated with depth-dependent local strain rates at both low and high strain rates. Moreover, when the surface layer was removed, both depth-dependence in dead cell distributions and in local strain rates disappeared at low and high strain rates. Although the mechanisms underlying mechanically induced osteoarthritis are still elusive, those results suggest a correlation between local chondrocyte death and transient strain rates in a depth dependent manner, and the surface layer played a crucial role in regulating chondrocyte damages and local strains in middle and deep layers. Our study, therefore, could contribute to an analytical understanding of cartilage degeneration under excessive stress loadings.
暴露于过度应激与骨关节炎的发病机制有关，骨关节炎是一种涉及关节软骨退变的关节疾病。已知成熟关节软骨的力学性能具有深度区域依赖性。尽管在体外过度应激加载后在关节软骨中观察到软骨细胞死亡，但很少有研究以深度依赖的方式研究软骨细胞死亡与局部机械应变之间的相关性。在这里，我们开发了一种实时观察系统，用于在显微镜载物台上以低（3.5%/秒）和高（35%/秒）应变率对切割后的软骨样本施加过度应激加载（18兆帕），这在体内被视为有害压缩。使用该系统，在压缩过程中对局部变形进行实时监测，并在短期培养后研究局部软骨细胞死亡情况。结果表明，在高应变率下，死亡细胞主要出现在表层。相比之下，在低应变率下，死亡细胞并非集中在表层，而是相对集中在中层。局部应变测量表明，在低应变率和高应变率下，死亡细胞分布均与深度依赖性局部应变率相关。此外，当去除表层时，在低应变率和高应变率下，死亡细胞分布和局部应变率的深度依赖性均消失。尽管机械性诱导骨关节炎的潜在机制仍不清楚，但这些结果表明局部软骨细胞死亡与瞬时应变率之间存在深度依赖的相关性，并且表层在调节中层和深层的软骨细胞损伤和局部应变方面起着关键作用。因此，我们的研究有助于对过度应激负荷下软骨退变进行分析性理解。
