TNF-related apoptosis-inducing ligand (TRAIL) blocks osteoclastic differentiation induced by RANKL plus M-CSF

摘要: The role of the tumor necrosis factor (TNF) superfamily member receptor activator nuclear kappa B ligand (RANKL) in promoting differentiation osteoclasts has been extensively characterized. In this study, we have investigated effect TNF-related apoptosis-inducing (TRAIL), a TNF cytokines, osteoclastogenesis, by using human peripheral blood mononuclear cells and RAW264.7 murine monocytic cell line. Both models differentiate into osteoclast-like presence RANKL plus macrophage-colony-stimulating (M-CSF), as evaluated terms tartrate-resistant acid phosphatase (TRAP)-positive multinucleated bone resorption activity. Unexpectedly, when added culture combination with M-CSF, TRAIL inhibited osteoclastic both models. To investigate molecular mechanism underlining such inhibitory activity, analyzed on mitogen-activated protein kinases (MAPKs) pathways, which play key osteoclastogenesis. Treatment M-CSF activated ERK1/2 p38/MAPK are essential for proliferation preosteoclasts, respectively. Of note, addition to did not affect but it profoundly phosphorylation. Thus, our data demonstrate that blocks suggest inhibition pathway likely plays an important process. (Blood. 2004;104:2044-2050)