Apoptotic chondrocyte death in rheumatoid arthritis.

Abstract

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.