Human osteoblasts are resistant to Apo2L/TRAIL-mediated apoptosis

Osteoblasts Display Different Responsiveness to TRAIL-Induced Apoptosis During Their Differentiation Process

“…We demonstrated that undifferentiated OBs are sensitive, whereas differentiated ones are resistant to TRAIL-apoptotic effect. Up to now, literature data have reported conflicting results concerning the apoptotic role of TRAIL in osteoblastic cells [8][9][10][11][12][13][14]. In particular, it has been demonstrated that some osteosarcoma cell lines are resistant to TRAIL apoptotic effect while others are sensitive [8,11].…”

“…Up to now, literature data have reported conflicting results concerning the apoptotic role of TRAIL in osteoblastic cells [8][9][10][11][12][13][14]. In particular, it has been demonstrated that some osteosarcoma cell lines are resistant to TRAIL apoptotic effect while others are sensitive [8,11]. In addition, their responsiveness to TRAIL could also change, this is the case of the BTK-143 osteogenic sarcoma cells, which can gradually acquire TRAIL resistance due to progressive acquisition of the DcR2 [12], or that of MG 63 osteosarcoma cells which undergo apoptosis in response to DR5 agonist [10].…”

“…As apoptosis of bone cells is a rapid process and cannot be assessed in vivo during bone turnover in a normal adult organism [5], expression and function of apoptotic molecules, belonging to tumor necrosis factor (TNF) ligand and receptor families, have been investigated on bone cells in vitro, with controversial results from different experimental models and methods [1,6,7]. Among the members of the TNF family, some authors have examined the sensitivity of OBs to TNF-related apoptosis-inducing ligand (TRAIL), but contradictory results have also emerged from these studies [8][9][10][11][12][13][14].…”

Agonists of TRAIL death receptors induce myeloma cell apoptosis that is not prevented by cells of the bone marrow microenvironment

“…7 Whilst it has been suggested that expression of the decoy receptors may confer TRAIL resistance, a clear correlation between expression of TRAIL receptors and response to TRAIL has not been demonstrated. 5,[8][9][10] Recent studies have shown that another member of the TNF receptor superfamily, osteoprotegerin (OPG), which is expressed by osteoblasts and bone marrow stromal cells, can function as a soluble decoy receptor for TRAIL. 11,12 In support of this, we have previously shown that OPG can protect myeloma cells against TRAIL-induced apoptosis, suggesting that OPG may function as a paracrine survival factor in the bone marrow microenvironment.…”

Progressive resistance of BTK-143 osteosarcoma cells to Apo2L/TRAIL-induced apoptosis is mediated by acquisition of DcR2/TRAIL-R4 expression: resensitisation with chemotherapy

“…Apo2L/TRAIL is a new member of the tumour necrosis factor (TNF)-cytokine family that induces cell death in a wide variety of tumour cell lines, but does not seem to be cytotoxic to many normal cell types in vitro or in vivo (Ashkenazi et al, 1999;Walczak et al, 1999;Atkins et al, 2002;Evdokiou et al, 2002). Apo2L/TRAIL is a type II transmembrane protein that induces apoptosis through interactions with its death domain-containing receptors, DR4/TRAIL-R1 and DR5/TRAIL-R2 (Pan et al, 1997a,b;Sheridan et al, 1997;Walczak et al, 1997).…”