Cellular events leading to chondrocyte death after cartilage impact injury
Cellular events leading to chondrocyte death after cartilage impact injury
复制标题
DOI：
10.1002/art.21812
复制
发表时间：
2006-05-01
影响因子：
--
通讯作者：
Birdsall, H. H.
中科院分区：
文献类型：
--
作者：
Green, D. M.;Noble, P. C.;Birdsall, H. H.
目标。我们进行了这项研究，以验证我们的假设，即白细胞在急性机械创伤后延伸到软骨损伤区域。新鲜犬股骨髁受到20~25兆帕的冲击性损伤。将关节突外植体或分散的软骨细胞与自体血单个核细胞(MNL)共同培养。台盼蓝拒染法检测不同距离撞击部位软骨细胞的活性。机械损伤会在7天内造成大量存活软骨细胞的丧失，即使是在距撞击部位10 mm的软骨中也是如此。在生物力学应激后，加入N-G-单甲基精氨酸抑制一氧化氮(NO)的生成，可在很大程度上防止撞击后10 mm以内的细胞死亡。撞击10 mm以内的软骨细胞也容易被活的MNL杀死，但不能与内毒素激活的MNL上清液孵育。在这个脆弱区域的软骨细胞表达细胞间黏附分子1(ICAM-1)(CD54)，促进定位于软骨细胞附近的单核细胞的附着。白细胞通过产生活性氧杀死从冲击区采集的分散的软骨细胞。白细胞介导的杀伤可被去铁胺或CD18抗体阻断，后者可阻止白细胞与表达ICAM 1的软骨细胞黏附。我们的数据表明，机械损伤后，远离部位的软骨细胞可能通过产生NO而被杀死。炎性白细胞通过黏附表达ICAM-1的软骨细胞和诱导氧自由基在软骨细胞胞浆中积累，进一步扩大了软骨细胞的死亡区域。患者可以从减少炎症白细胞向急性损伤的软骨渗透的治疗中受益。
Objective. We undertook this study to test our postulate that leukocytes extend the zone of injury in cartilage after acute mechanical trauma.Methods. Fresh cadaveric canine femoral condyles were subjected to 20-25-MPa impact injury. Condyle explants or dispersed chondrocytes were cultured with autologous blood mononuclear leukocytes (MNLs). Viability of chondrocytes at varying distances from the impact site was assessed by trypan blue exclusion.Results. Mechanical injury caused a significant loss of viable chondrocytes over 7 days, even in cartilage > 10 mm from the impact site. After biomechanical stress, death of cells within 10 mm of the impact could be largely prevented by addition of N-G-monomethyl-Larginine to inhibit nitric oxide (NO) generation. Chondrocytes within 10 mm of the impact were also susceptible to killing by living MNLs, but not by incubation with the supernatants of endotoxin-activated MNLs. Chondrocytes in this vulnerable zone expressed intercellular adhesion molecule 1 (ICAM-1) (CD54), facilitating attachment of MNLs that localized adjacent to the chondrocytes. Leukocytes killed dispersed chondrocytes harvested from the impact zone by generation of reactive oxygen species. Leukocyte-mediated killing could be blocked by desferoxamine or by antibodies to CD18, which prevent attachment of leukocytes to ICAM1-expressing chondrocytes.Conclusion. Our data suggest that after mechanical injury, chondrocytes distant from the site may be killed through the generation of NO. Inflammatory leukocytes further extend the zone of chondrocyte death by adhering to chondrocytes expressing ICAM-1 and by inducing the accumulation of free oxygen radicals in the chondrocyte cytoplasm. Patients may benefit from therapies that reduce infiltration of inflammatory leukocytes into acutely injured cartilage.