TY - JOUR
T1 - Osteoblasts Display Different Responsiveness to TRAIL-Induced Apoptosis During Their Differentiation Process
AU - Brunetti, Giacomina
AU - Oranger, Angela
AU - Carbone, Claudia
AU - Mori, Giorgio
AU - Sardone, Francesca Rita
AU - Mori, Claudio
AU - Celi, Monica
AU - Faienza, Maria Felicia
AU - Tarantino, Umberto
AU - Zallone, Alberta
AU - Grano, Maria
AU - Colucci, Silvia
PY - 2013/12
Y1 - 2013/12
N2 - Apoptosis can occur throughout the life span of osteoblasts (OBs), beginning from the early stages of differentiation and continuing throughout all stages of their working life. Here, we investigated the effects of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on normal human OBs showing for the first time that the expression of TRAIL receptors is modulated during OB differentiation. In particular, the TRAIL receptor ratio was in favor of the deaths because of the low expression of DcR2 in undifferentiated OBs, differently it was shifted toward the decoys in differentiated ones. Undifferentiated OBs treated with TRAIL showed reduced cell viability, whereas differentiated OBs displayed TRAIL resistance. The OB sensitiveness to TRAIL was due to the up-regulation of DR5 and the down-regulation of DcR2. The main death receptor involved in TRAIL-reduced OB viability was DR5 as demonstrated by the rescue of cell viability observed in the presence of anti-DR5 neutralizing antibody. Besides the ratio of TRAIL receptors, the sensitivity of undifferentiated OBs to TRAIL-cytotoxic effect was also associated with low mRNA levels of intracellular anti-apoptotic proteins, such as cFLIP, the activation of caspase-8 and -3, as well as the DNA fragmentation. This study suggests that apoptotic effect exerted by TRAIL/TRAIL-receptor system on normal human OB is strictly dependent upon cell differentiation status.
AB - Apoptosis can occur throughout the life span of osteoblasts (OBs), beginning from the early stages of differentiation and continuing throughout all stages of their working life. Here, we investigated the effects of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on normal human OBs showing for the first time that the expression of TRAIL receptors is modulated during OB differentiation. In particular, the TRAIL receptor ratio was in favor of the deaths because of the low expression of DcR2 in undifferentiated OBs, differently it was shifted toward the decoys in differentiated ones. Undifferentiated OBs treated with TRAIL showed reduced cell viability, whereas differentiated OBs displayed TRAIL resistance. The OB sensitiveness to TRAIL was due to the up-regulation of DR5 and the down-regulation of DcR2. The main death receptor involved in TRAIL-reduced OB viability was DR5 as demonstrated by the rescue of cell viability observed in the presence of anti-DR5 neutralizing antibody. Besides the ratio of TRAIL receptors, the sensitivity of undifferentiated OBs to TRAIL-cytotoxic effect was also associated with low mRNA levels of intracellular anti-apoptotic proteins, such as cFLIP, the activation of caspase-8 and -3, as well as the DNA fragmentation. This study suggests that apoptotic effect exerted by TRAIL/TRAIL-receptor system on normal human OB is strictly dependent upon cell differentiation status.
KW - Apoptosis
KW - c-FLIP
KW - DcR2
KW - Osteoblast
KW - TRAIL
KW - TRAIL receptor
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UR - http://www.scopus.com/inward/citedby.url?scp=84877595728&partnerID=8YFLogxK
U2 - 10.1007/s12013-013-9616-6
DO - 10.1007/s12013-013-9616-6
M3 - Article
AN - SCOPUS:84877595728
VL - 67
SP - 1127
EP - 1136
JO - Cell Biochemistry and Biophysics
JF - Cell Biochemistry and Biophysics
SN - 1085-9195
IS - 3
ER -