Impact of mechanical trauma on matrix and cells
Impact of mechanical trauma on matrix and cells
复制标题
DOI：
10.1097/00003086-200110001-00009
复制
发表时间：
2001-10-01
影响因子：
4.2
通讯作者：
Lotz, MK
中科院分区：
文献类型：
--
作者：
D'Lima, DD;Hashimoto, S;Lotz, MK
创伤后关节炎是继发性骨关节炎最常见的原因之一。细胞死亡对基质降解的贡献尚未完全表征。本研究旨在确定机械损伤对软骨细胞活力和基质降解的影响。使直径为5 mm的全层牛和人软骨外植体经受代表创伤性关节损伤的机械载荷。测量糖胺聚糖释放和凋亡细胞百分比。对8只麻醉家兔的单侧髌骨进行冲击载荷试验。在损伤后96小时对兔实施安乐死，并收获髌骨软骨用于分析。测定了泛半胱天冬酶抑制剂z-VAD. fetamine [苄氧基羰基-Val-Ala-Asp（OMe）氟甲基酮]在人关节软骨外植体中预防软骨细胞凋亡的作用。观察到响应于机械负荷的凋亡细胞数量的显著增加。对照组和嵌顿组的平均凋亡率分别为1%和15%。机械损伤后，半胱天冬酶抑制剂使软骨细胞凋亡从34%减少到25%，并与糖胺聚糖释放减少相关。机械损伤诱导软骨细胞凋亡，对药物抑制敏感。这确定了一种新的方法，以限制创伤性软骨损伤和继发性骨关节炎的后续发展。
Posttraumatic arthritis is one of the most common causes of secondary osteoarthritis. The contribution of cell death to matrix degradation has not been characterized fully. The current study was designed to determine the effect of mechanical injury on chondrocyte viability and matrix degradation. Full-thickness bovine and human cartilage explants, 5 mm in diameter were subjected to mechanical loads representative of traumatic joint injury. Glycosaminoglycan release and percent apoptotic cells were measured. Unilateral patellas in eight anesthetized rabbits were subjected to an impact load. Rabbits were euthanized at 96 hours after injury and patellar cartilage was harvested for analysis. The effect of a pan-caspase inhibitor, z-VAD.fmk [benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone] in preventing chondrocyte apoptosis in human articular cartilage explants was determined. A significant increase in the number of apoptotic cells was observed in response to mechanical loading. The mean in vivo apoptotic rates were 1% in control rabbits and 15% in impacted patellas. Caspase inhibition reduced chondrocyte apoptosis from 34% to 25% after mechanical injury and was associated with reduction in glycosaminoglycan release. Mechanical injury induces chondrocyte apoptosis that is sensitive to pharmacologic inhibition. This identifies a new approach to limit traumatic cartilage injury and the subsequent development of secondary osteoarthritis.