Involvement of SOCS3 in regulation of CD11c+ dendritic cell-derived osteoclastogenesis and severe alveolar bone loss.
Infect Immun
; 77(5): 2000-9, 2009 May.
Article
em En
| MEDLINE
| ID: mdl-19255186
ABSTRACT
To investigate the role of suppressor of cytokine signaling (SOCS) molecules in periodontal immunity and RANKL-mediated dendritic cell (DC)-associated osteoclastogenesis, we analyzed SOCS expression profiles in CD4(+) T cells and the effect of SOCS3 expression in CD11c(+) DCs during periodontal inflammation-induced osteoclastogenesis and bone loss in nonobese diabetic (NOD) versus humanized NOD/SCID mice. Our results of ex vivo and in vitro analyses showed that (i) there is significantly higher SOCS3 expression associated with RANKL(+) T-cell-mediated bone loss in correlation with increased CD11c(+) DC-mediated osteoclastogenesis; (ii) the transfection of CD11c(+) DC using an adenoviral vector carrying a dominant negative SOCS3 gene significantly abrogates TRAP and bone-resorptive activity; and (iii) inflammation-induced TRAP expression, bone resorption, and SOCS3 activity are not associated with any detectable change in the expression levels of TRAF6 and mitogen-activated protein kinase signaling adaptors (i.e., Erk, Jnk, p38, and Akt) in RANKL(+) T cells. We conclude that SOCS3 plays a critical role in modulating cytokine signaling involved in RANKL-mediated DC-derived osteoclastogenesis during immune interactions with T cells and diabetes-associated severe inflammation-induced alveolar bone loss. Therefore, the development of SOCS3 inhibitors may have therapeutic potential as the target to halt inflammation-induced bone loss under pathological conditions in vivo.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Reabsorção Óssea
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Células Dendríticas
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Infecções por Actinobacillus
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Perda do Osso Alveolar
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Aggregatibacter actinomycetemcomitans
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Proteínas Supressoras da Sinalização de Citocina
Limite:
Adult
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Animals
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Female
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Humans
Idioma:
En
Revista:
Infect Immun
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos