Apoptotic chondrocyte death in rheumatoid arthritis

Objective, Recently, chondrocytes were shown to undergo apoptosis by the ad dition of nitric oxide and by coupling of Fas/Fas ligand in vitro, suggesti ng the possibility that chondrocytes have an inherent programmed cell death pathway that operates in adult cartilage. Chondrocyte apoptosis was verifi ed in situ in articular cartilage samples from humans with osteoarthritis ( OA) and from an animal model of OA, The present study investigates apoptoti c chondrocyte death and the expression of Bcl-2 and Fas in rheumatoid arthr itis (RA) cartilage. Methods. 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 ca rtilage specimens. Apoptosis was verified by TUNEL, electron microscopy, an d DNA ladder assay. Bcl-2 and Fas expression were evaluated by immunohistoc hemistry. Results. Apoptotic cells were frequently observed in Ri cartilage, whereas normal cartilage rarely showed apoptotic cells (3.01% versus 0.15%, respect ively), a finding that was further confirmed by TUNEL staining. On electron microscopy, numerous apoptotic cells with typical chromatin condensation w ere observed in RA cartilage. DNA from RA cartilage also revealed 180-basep air nucleosome ladders on electrophoresis. Bcl-2 expression was significant ly lower in RA cartilage than in normal cartilage (23.3% versus 43.1%, resp ectively), whereas Fas expression was not statistically different. Conclusion. 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.