Selective inhibition of NF-kappa B blocks osteoclastogenesis and prevents inflammatory bone destruction in vivo.
Nat Med
; 10(6): 617-24, 2004 Jun.
Article
em En
| MEDLINE
| ID: mdl-15156202
ABSTRACT
Bone destruction is a pathological hallmark of several chronic inflammatory diseases, including rheumatoid arthritis and periodontitis. Inflammation-induced bone loss of this sort results from elevated numbers of bone-resorbing osteoclasts. Gene targeting studies have shown that the transcription factor nuclear factor-kappa B (NF-kappa B) has a crucial role in osteoclast differentiation, and blocking NF-kappa B is a potential strategy for preventing inflammatory bone resorption. We tested this approach using a cell-permeable peptide inhibitor of the I kappa B-kinase complex, a crucial component of signal transduction pathways to NF-kappa B. The peptide inhibited RANKL-stimulated NF-kappa B activation and osteoclastogenesis both in vitro and in vivo. In addition, this peptide significantly reduced the severity of collagen-induced arthritis in mice by reducing levels of tumor necrosis factor-alpha and interleukin-1 beta, abrogating joint swelling and reducing destruction of bone and cartilage. Therefore, selective inhibition of NF-kappa B activation offers an effective therapeutic approach for inhibiting chronic inflammatory diseases involving bone resorption.
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Bases de dados:
MEDLINE
Assunto principal:
Osteoclastos
/
Peptídeos
/
Osso e Ossos
/
Reabsorção Óssea
/
NF-kappa B
/
Proteínas I-kappa B
/
Inflamação
Limite:
Animals
Idioma:
En
Revista:
Nat Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos