title: Osteoblasts display different responsiveness to TRAIL-induced apoptosis during their differentiation process.
abstract: 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.
authors.affiliation: Section of Human Anatomy and Histology - R. Amprino, Department of Basic Medical Sciences, Neuroscience and Sense Organs, Medical School, University of Bari, Piazza Giulio Cesare 11, 70124, Bari, Italy.
authors.forename: Giacomina
authors.initials: G
authors.lastname: Brunetti
authors.forename: Angela
authors.initials: A
authors.lastname: Oranger
authors.forename: Claudia
authors.initials: C
authors.lastname: Carbone
authors.forename: Giorgio
authors.initials: G
authors.lastname: Mori
authors.forename: Francesca Rita
authors.initials: FR
authors.lastname: Sardone
authors.forename: Claudio
authors.initials: C
authors.lastname: Mori
authors.forename: Monica
authors.initials: M
authors.lastname: Celi
authors.forename: Maria Felicia
authors.initials: MF
authors.lastname: Faienza
authors.forename: Umberto
authors.initials: U
authors.lastname: Tarantino
authors.forename: Alberta
authors.initials: A
authors.lastname: Zallone
authors.forename: Maria
authors.initials: M
authors.lastname: Grano
authors.forename: Silvia
authors.initials: S
authors.lastname: Colucci
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000633:toxicity*; D053319:Tumor Necrosis Factor Decoy Receptors / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D057134:Antibodies, Neutralizing; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C451501:TNFRSF10D protein, human; D053319:Tumor Necrosis Factor Decoy Receptors; D004247:DNA; D053148:Caspase 3; D053181:Caspase 8