Injurious mechanical compression of bovine articular cartilage induces chondrocyte apoptosis
Injurious mechanical compression of bovine articular cartilage induces chondrocyte apoptosis
复制标题
牛关节软骨的损伤性机械挤压诱导软骨细胞凋亡
DOI：
10.1006/abbi.2000.1988
复制
发表时间：
2000-09-15
影响因子：
3.9
通讯作者：
Lark, MW
中科院分区：
文献类型：
--
作者：
Loening, AM;James, IE;Lark, MW
采用牛软骨移植系统研究损伤性压缩对软骨细胞凋亡和软骨基质生物化学及生物力学特性的影响。将新生牛关节软骨的软骨在体外压缩到各种峰值应力水平，并对软骨细胞凋亡细胞死亡、组织生物力学特性、组织肿胀、糖胺聚糖损失和亚硝酸盐水平进行定量。软骨细胞凋亡发生在峰值应力低至4.5 MPa，并增加与峰值应力的剂量依赖性的方式。这种细胞凋亡的增加在加载方案终止后24小时达到最大。在高峰应力（>20 MPa）下，大于50%的细胞发生断裂。当在单轴侧限压缩测量时，外植体的平衡和动态刚度随着损伤载荷的严重程度而降低，尽管这种趋势在24 MPa峰值应力之前并不显著，相反，在径向无侧限压缩测量的平衡和动态刚度在12和7 MPa的损伤应力之后分别显著降低。总之，这些结果表明，在7- 12-MPa范围内，有害压缩导致胶原纤维网络降解。与这一假设相一致，损伤性压缩导致组织肿胀的剂量依赖性增加，在13 MPa峰值应力下显著。糖胺聚糖也以剂量依赖性的方式从软骨中释放，在6- 13-MPa的峰值应力下显著。亚硝酸盐水平显着增加，高于对照组在20 MPa的峰值应力。总之，这些数据表明，有害的压缩可以刺激细胞死亡，以及一系列的生物力学和生物化学改变的矩阵，并可能，软骨细胞一氧化氮的表达。有趣的是，软骨细胞程序性细胞死亡似乎发生在低于刺激软骨基质降解和生物力学变化所需的应力下。虽然软骨细胞凋亡因此可能是对组织损伤的最早反应之一，但目前尚不清楚这种最初的细胞反应是否随后驱动软骨基质降解和组织生物力学性质的变化。(C)北京大学出版社.
A bovine cartilage explant system was used to evaluate the effects of injurious compression on chondrocyte apoptosis and matrix biochemical and biomechanical properties within intact cartilage. Disks of newborn bovine articular cartilage were compressed in vitro to various peak stress levels and chondrocyte apoptotic cell death, tissue biomechanical properties, tissue swelling, glycosaminoglycan loss, and nitrite levels were quantified. Chondrocyte apoptosis occurred at peak stresses as low as 4.5 MPa and increased with peak stress in a dose-dependent manner. This increase in apoptosis was maximal by 24 h after the termination of the loading protocol. At high peak stresses (>20 MPa), greater than 50%, of cells apoptosed. When measured in uniaxial confined compression, the equilibrium and dynamic stiffness of explants decreased with the severity of injurious load, although this trend was not significant until 24-MPa peak stress, In contrast, the equilibrium and dynamic stiffness measured in radially unconfined compression decreased significantly after injurious stresses of 12 and 7 MPa, respectively. Together, these results suggested that injurious compression caused a degradation of the collagen fibril network in the 7- to 12-MPa range. Consistent with this hypothesis, injurious compression caused a dose-dependent increase in tissue swelling, significant by 13-MPa peak stress. Glycosaminoglycans were also released from the cartilage in a dose-dependent manner, significant by 6- to 13-MPa peak stress. Nitrite levels were significantly increased above controls at 20-MPa peak stress. Together, these data suggest that injurious compression can stimulate cell death as well as a range of biomechanical and biochemical alterations to the matrix and, possibly, chondrocyte nitric oxide expression. Interestingly, chondrocyte programmed cell death appears to take place at stresses lower than those required to stimulate cartilage matrix degradation and biomechanical changes. While chondrocyte apoptosis may therefore be one of the earliest responses to tissue injury, it is currently unclear whether this initial cellular response subsequently drives cartilage matrix degradation and changes in the biomechanical properties of the tissue. (C) 2000 Academic Press.