Kim H A, Song Y W
Seoul National University College of Medicine, Korea.
Arthritis Rheum. 1999 Jul;42(7):1528-37. doi: 10.1002/1529-0131(199907)42:7<1528::AID-ANR28>3.0.CO;2-9.
Recently, chondrocytes were shown to undergo apoptosis by the addition of nitric oxide and by coupling of Fas/Fas ligand in vitro, suggesting the possibility that chondrocytes have an inherent programmed cell death pathway that operates in adult cartilage. Chondrocyte apoptosis was verified in situ in articular cartilage samples from humans with osteoarthritis (OA) and from an animal model of OA. The present study investigates apoptotic chondrocyte death and the expression of Bcl-2 and Fas in rheumatoid arthritis (RA) cartilage.
Cartilage samples were obtained from 13 RA patients at the time of joint replacement surgery and from 8 normal subjects at autopsy. Apoptotic chondrocytes were observed and counted in hematoxylin and eosin-stained cartilage specimens. Apoptosis was verified by TUNEL, electron microscopy, and DNA ladder assay. Bcl-2 and Fas expression were evaluated by immunohistochemistry.
Apoptotic cells were frequently observed in RA cartilage, whereas normal cartilage rarely showed apoptotic cells (3.01% versus 0.15%, respectively), a finding that was further confirmed by TUNEL staining. On electron microscopy, numerous apoptotic cells with typical chromatin condensation were observed in RA cartilage. DNA from RA cartilage also revealed 180-basepair nucleosome ladders on electrophoresis. Bcl-2 expression was significantly lower in RA cartilage than in normal cartilage (23.3% versus 43.1%, respectively), whereas Fas expression was not statistically different.
Apoptotic chondrocyte death and decreased Bcl-2 expression were verified in RA cartilage. They might provide a novel model system for the research of cartilage breakdown and joint destruction in RA.
最近研究表明，在体外添加一氧化氮以及通过Fas/Fas配体偶联可使软骨细胞发生凋亡，这提示软骨细胞可能存在一种内在的程序性细胞死亡途径，该途径在成年软骨中发挥作用。在骨关节炎（OA）患者以及OA动物模型的关节软骨样本中已证实存在软骨细胞凋亡。本研究调查类风湿关节炎（RA）软骨中凋亡软骨细胞死亡情况以及Bcl-2和Fas的表达。
在关节置换手术时从13例RA患者获取软骨样本，并在尸检时从8例正常受试者获取软骨样本。在苏木精和伊红染色的软骨标本中观察并计数凋亡软骨细胞。通过末端脱氧核苷酸转移酶介导的缺口末端标记法（TUNEL）、电子显微镜检查和DNA梯状条带分析来验证细胞凋亡。通过免疫组织化学评估Bcl-2和Fas的表达。
在RA软骨中经常观察到凋亡细胞，而正常软骨很少显示凋亡细胞（分别为3.01%和0.15%），这一发现通过TUNEL染色得到进一步证实。电子显微镜检查显示，RA软骨中有大量具有典型染色质凝聚的凋亡细胞。RA软骨的DNA在电泳时也显示出180碱基对的核小体梯状条带。RA软骨中Bcl-2的表达明显低于正常软骨（分别为23.3%和43.1%），而Fas的表达无统计学差异。
在RA软骨中证实存在凋亡软骨细胞死亡以及Bcl-2表达降低。它们可能为研究RA中软骨破坏和关节破坏提供一个新的模型系统。
