Pim-1 regulates RANKL-induced osteoclastogenesis via NF-κB activation and NFATc1 induction.
J Immunol
; 185(12): 7460-6, 2010 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-21068407
ABSTRACT
Pim kinases are emerging as important mediators of cytokine signaling pathways in hematopoietic cells. In this study, we demonstrate that Pim-1 positively regulates RANKL-induced osteoclastogenesis and that Pim-1 expression can be upregulated by RANKL signaling during osteoclast differentiation. The silencing of Pim-1 by RNA interference or overexpression of a dominant negative form of Pim-1 (Pim-1 DN) in bone marrow-derived macrophage cells attenuates RANKL-induced osteoclast formation. Overexpression of Pim-1 DN blocks RANKL-induced activation of TGF-ß-activated kinase 1 (TAK1) and NF-κB as well as expression of NFATc1 during osteoclastogenesis. However, we found that overexpression of TAK1 in the presence of Pim-1 DN rescues NF-κB activation. Additionally, Pim-1 interacts with RANK as well as TAK1, indicating that Pim-1 is involved in RANKL-induced NF-κB activation via TAK1. Furthermore, we demonstrate that Pim-1 also regulates NFATc1 transcription activity and subsequently induces osteoclast-associated receptor expression, an osteoclast-specific gene. Taken together, our results reveal that Pim-1 positively regulates RANKL-induced osteoclastogenesis.
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Base de dados:
MEDLINE
Assunto principal:
Osteoclastos
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Diferenciação Celular
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NF-kappa B
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Proteínas Proto-Oncogênicas c-pim-1
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Fatores de Transcrição NFATC
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Ligante RANK
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article