Tumor necrosis factor-related apoptosis-inducing ligand induces apoptosis in human articular chondrocytes in vitro.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is produced by immune cells and by mediating apoptosis, TRAIL plays an important role in tumor surveillance. TRAIL binds four different membrane-bound receptors: DR4, DR5, DcR1, and DcR2. The DR4- and DR5-receptors mediate apoptosis, whereas the others do not. We demonstrated by reverse transcriptase-polymerase chain reaction and flow cytometry that, in vitro, normal human articular chondrocytes express the receptors mediating apoptosis (DR4 and DR5) and one of the decoy receptors (DcR2). Also, we demonstrated that chondrocytes were subjected to cell death within few hours after challenge with TRAIL and that cytotoxicity was dose-dependent. Treated cells had apoptotic morphology accompanied by active caspase-3 immunoreactivity. These data indicate that normal human articular chondrocytes are susceptible to TRAIL-mediated apoptosis, which otherwise is typical for transformed cells, and also that death receptors and their respective ligands may have a crucial role in cartilage generation and destruction.
Pettersen
I
I
Department of Experimental Pathology, Medical Faculty, University of Tromsö, N-9037 Tromsö, Norway.
Figenschau
Y
Y
Olsen
E
E
Bakkelund
W
W
Smedsröd
B
B
Sveinbjörnsson
B
B
D000328:Adult; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002358:Cartilage, Articular / Q000166:cytology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases