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损伤性压缩对小牛关节软骨外植体中单个细胞周围基质周转的影响。

Effects of injurious compression on matrix turnover around individual cells in calf articular cartilage explants.

作者信息

Quinn T M, Grodzinsky A J, Hunziker E B, Sandy J D

机构信息

Center for Biomedical Engineering, Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge 02139, USA.

出版信息

J Orthop Res. 1998 Jul;16(4):490-9. doi: 10.1002/jor.1100160415.

Abstract

The effects of mechanical injury on the metabolism of cartilage matrix are of interest for understanding the pathogenesis of osteoarthrosis and the development of strategies for cartilage repair. The purpose of the present study was to examine the effects of injury on matrix turnover in a calf articular cartilage explant system for which the effects of mechanical loading on cell activity and the cell-mediated pathways of matrix metabolism are already well characterized. New methods of quantitative autoradiography were used in combination with established biochemical and biomechanical techniques for the analysis of cell and matrix responses to acute mechanical injury, with particular attention to the processes of localized matrix turnover in the cell-associated matrices of individual chondrocytes. Matrix deposition and turnover around cells in control explants was spatially dependent, with the highest rates of proteoglycan deposition and turnover and the lowest rates of collagen deposition (as indicated by [3H]proline autoradiography) occurring in the pericellular matrix. Injurious compression was associated with (a) an abrupt decrease in the tensile load-carrying capacity of the collagen matrix, apparently associated with mechanical failure of the tissue, (b) a considerable but subtotal decrease in cell viability, marked by the emergence of an apparently inactive cell population interspersed within catabolically active but abnormally large cells, and (c) sustained, elevated rates of proteoglycan turnover, particularly in the cell-associated matrices of apparently viable cells, which involved the increased release of aggregating species in addition to a spectrum of degradation fragments that were also in controls. These results may represent an in vitro model for the responses of chondrocytes and the cartilage extracellular matrix to mechanical injury.

摘要

机械损伤对软骨基质代谢的影响,对于理解骨关节炎的发病机制以及软骨修复策略的开发具有重要意义。本研究的目的是在小牛关节软骨外植体系统中,研究损伤对基质周转的影响,在该系统中,机械负荷对细胞活性和基质代谢的细胞介导途径的影响已得到充分表征。定量放射自显影的新方法与既定的生化和生物力学技术相结合,用于分析细胞和基质对急性机械损伤的反应,特别关注单个软骨细胞的细胞相关基质中局部基质周转的过程。对照外植体中细胞周围的基质沉积和周转在空间上是依赖的,蛋白聚糖沉积和周转速率最高,而胶原蛋白沉积速率最低(如[3H]脯氨酸放射自显影所示),发生在细胞周围基质中。损伤性压缩与以下情况相关:(a) 胶原基质的拉伸承载能力突然下降,显然与组织的机械故障有关;(b) 细胞活力显著但不完全下降,表现为出现明显不活跃的细胞群体,散布在分解代谢活跃但异常大的细胞中;(c) 蛋白聚糖周转速率持续升高,特别是在明显存活细胞的细胞相关基质中,这除了涉及一系列在对照中也存在的降解片段外,还包括聚集物种释放增加。这些结果可能代表了软骨细胞和软骨细胞外基质对机械损伤反应的体外模型。

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