Studies on the contribution of c-fos/AP-1 to arthritic joint destruction.
J Clin Invest
; 99(6): 1210-6, 1997 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-9077528
ABSTRACT
Features characteristic to rheumatoid joint destruction, including synovial overgrowth and bone resorption, are experimentally produced by augmenting c-fos gene expression. We tested here if arthritic joint destruction was inhibited upon inactivation of the c-fos/AP-1 signal by administering short double-stranded AP-1 DNA oligonucleotides into mice with collagen-induced arthritis to compete for the binding of AP-1 in vivo at the promoter binding site. Arthritic joint destruction was inhibited in a sequence-specific and dose-dependent manner by oligonucleotides containing the AP-1 sequence. The oligonucleotides inhibited gene expression at the transcriptional level. Nucleotide sequences besides AP-1 also appeared to be important structurally for binding of AP-1 onto DNA and for the stability of oligonucleotides against nucleases. Immunohistochemical chase experiment administering biotinylated oligonucleotides into arthritic mice showed that AP-1 oligonucleotides reached the inflamed joint. Thus, activation of c-fos/AP-1 appears essentially important in arthritic joint destruction.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite
/
Proteínas Proto-Oncogênicas c-fos
/
Fator de Transcrição AP-1
Limite:
Animals
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Japão