Fas/Fas ligand expression and induction of apoptosis in chondrocytes.
OBJECTIVE
To examine the expression of Fas/Fas ligand and the role of this ligand/receptor interaction in the regulation of apoptosis in normal human articular chondrocytes and in osteoarthritis (OA) cartilage.


METHODS
Normal and OA human knee cartilage and cells isolated from these tissues were tested for Fas expression by flow cytometry. Induction of apoptosis by antibody to Fas was analyzed by DAPI staining and electron microscopy.


RESULTS
Treatment of freshly isolated normal human articular chondrocytes with an agonistic Fas antibody induced apoptosis in a subpopulation (approximately 20%) of the cells. Apoptosis induced by anti-Fas was not dependent on nitric oxide (NO), and anti-Fas also did not induce NO production. Analysis of isolated cells demonstrated similar levels of Fas expression on normal and OA chondrocytes (28% and 32%, respectively). In normal articular cartilage, Fas-positive cells were located mainly in the superficial and midzones. In contrast, in fibrillated OA cartilage, surface layers were partially absent and Fas-expressing cells were also detected in the deeper layers. Fas ligand messenger RNA was not detectable in resting or activated normal or OA chondrocytes. Analysis by electron microscopy showed the nuclear and cytoplasmic changes typical of apoptosis in cultures treated with antibody to Fas.


CONCLUSIONS
A subpopulation of chondrocytes expresses Fas and is susceptible to Fas-induced apoptosis. Fas-mediated chondrocyte apoptosis may contribute to cartilage degradation in arthritis.
Hashimoto
S
S
The Scripps Research Institute, La Jolla, California 92037, USA.
Setareh
M
M
Ochs
R L
RL
Lotz
M
M
D000906:Antibodies / Q000276:immunology; D017209:Apoptosis / Q000502:physiology*; D002356:Cartilage / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000276:immunology / Q000502:physiology* / Q000648:ultrastructure; D053222:Fas Ligand Protein; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D008854:Microscopy, Electron; D009569:Nitric Oxide / Q000502:physiology; D010003:Osteoarthritis / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D014018:Tissue Distribution; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism / Q000502:physiology*
D000906:Antibodies; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor; D009569:Nitric Oxide