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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11369/4163
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