Activin A inhibits RANKL-mediated osteoclast formation, movement and function in murine bone marrow macrophage cultures.
J Cell Sci
; 128(4): 683-94, 2015 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-25609708
ABSTRACT
The process of osteoclastic bone resorption is complex and regulated at multiple levels. The role of osteoclast (OCL) fusion and motility in bone resorption are unclear, with the movement of OCL on bone largely unexplored. RANKL (also known as TNFSF11) is a potent stimulator of murine osteoclastogenesis, and activin A (ActA) enhances that stimulation in whole bone marrow. ActA treatment does not induce osteoclastogenesis in stroma-free murine bone marrow macrophage cultures (BMM), but rather inhibits RANKL-induced osteoclastogenesis. We hypothesized that ActA and RANKL differentially regulate osteoclastogenesis by modulating OCL precursors and mature OCL migration. Time-lapse video microscopy measured ActA and RANKL effects on BMM and OCL motility and function. ActA completely inhibited RANKL-stimulated OCL motility, differentiation and bone resorption, through a mechanism mediated by ActA-dependent changes in SMAD2, AKT1 and inhibitor of nuclear factor κB (IκB) signaling. The potent and dominant inhibitory effect of ActA was associated with decreased OCL lifespan because ActA significantly increased activated caspase-3 in mature OCL and OCL precursors. Collectively, these data demonstrate a dual action for ActA on murine OCLs.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoclastos
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Reabsorção Óssea
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Fator Estimulador de Colônias de Macrófagos
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Ativinas
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Ligante RANK
Limite:
Animals
Idioma:
En
Revista:
J Cell Sci
Ano de publicação:
2015
Tipo de documento:
Article