TRAIL inhibits osteoclastic differentiation by counteracting RANKL-dependent p27Kip1 accumulation in pre-osteoclast precursors.
J Cell Physiol
; 214(1): 117-25, 2008 Jan.
Article
em En
| MEDLINE
| ID: mdl-17620297
ABSTRACT
Experimental evidences indicate that the TNF family member TNF-related apoptosis inducing ligand (TRAIL) might be involved in modulating osteoclastic differentiation. The ability of recombinant soluble TRAIL to affect bone density in vivo was evaluated by using 4-week-old mice subcutaneously (s.c.) injected with TRAIL for 8 days. TRAIL injection induced a significant increase of tibia trabecular thickness and total bone mass in 4-week-old mice, accompanied by a significant decrease of TRAP serum levels, without modulation of osteocalcin and osteoprotegerin (OPG). Parallel experiments performed in vitro showed that inhibition of osteoclastic differentiation, induced by treatment of human peripheral blood osteoclast precursors with TRAIL, was associated to inhibition of receptor activator of nuclear factor kappa B ligand (RANKL)-induced accumulation of p27(Kip1). The potential role of p27(Kip1) pathway in mediating the anti-osteoclastic activity of TRAIL was further suggested by in vitro gene knock-down experiments performed in osteoclast precursor cultures. Taken together, our data strongly suggest that recombinant TRAIL inhibits osteoclastogenesis by inducing the ubiquitin-mediated degradation of p27(Kip1).
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Bases de dados:
MEDLINE
Assunto principal:
Osteoclastos
/
Leucócitos Mononucleares
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Diferenciação Celular
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Inibidor de Quinase Dependente de Ciclina p27
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Ligante RANK
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Ligante Indutor de Apoptose Relacionado a TNF
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Cell Physiol
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Itália