Control of osteoclast (OC) apoptosis has been recognized as a critical regulatory factor in bone remodelling, and alteration in OC death and/or survival has been shown to contribute to the pathogenesis of osteoporosis or malignant osteolysis. TNF-related apoptosis-inducing ligand (TRAIL) has received considerable attention as a molecule showing the unique property to induce apoptosis in a variety of neoplastic cells, however, in many normal cells TRAIL can activate the apoptotic process. In this paper, we demonstrate for the first time a different TRAIL receptor expression pattern during OC differentiation. Moreover, we show that TRAIL treatment causes an increased apoptotic OC number, caspase 8 and 3 activation and the formation of the DNA ladder. The apoptotic process is mediated by death receptor 5 (DR5) as demonstrated by the increase in its expression following TRAIL treatment and by the rescue of the cell viability in OCs treated simultaneously with TRAIL and anti-DR5 neutralizing antibody. Elucidation of the mechanisms controlling OC apoptosis may reveal novel strategies for drug development.
Osteoclast apoptosis: Role of TRAIL and its receptors.
MORI, GIORGIO;
2009-01-01
Abstract
Control of osteoclast (OC) apoptosis has been recognized as a critical regulatory factor in bone remodelling, and alteration in OC death and/or survival has been shown to contribute to the pathogenesis of osteoporosis or malignant osteolysis. TNF-related apoptosis-inducing ligand (TRAIL) has received considerable attention as a molecule showing the unique property to induce apoptosis in a variety of neoplastic cells, however, in many normal cells TRAIL can activate the apoptotic process. In this paper, we demonstrate for the first time a different TRAIL receptor expression pattern during OC differentiation. Moreover, we show that TRAIL treatment causes an increased apoptotic OC number, caspase 8 and 3 activation and the formation of the DNA ladder. The apoptotic process is mediated by death receptor 5 (DR5) as demonstrated by the increase in its expression following TRAIL treatment and by the rescue of the cell viability in OCs treated simultaneously with TRAIL and anti-DR5 neutralizing antibody. Elucidation of the mechanisms controlling OC apoptosis may reveal novel strategies for drug development.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
