Regulation of the human ADAMTS-4 promoter by transcription factors and cytokines.
Biochem Biophys Res Commun
; 345(1): 197-204, 2006 Jun 23.
Article
en En
| MEDLINE
| ID: mdl-16677612
ABSTRACT
ADAMTS-4 (aggrecanase-1) is a metalloprotease that plays a role in aggrecan degradation in the cartilage extracellular matrix. In order to understand the regulation of ADAMTS-4 gene expression we have cloned and characterized a functional 4.5kb human ADAMTS-4 promoter. Sequence analysis of the promoter revealed the presence of putative binding sites for nuclear factor of activated T cells (NFAT) and Runx family of transcription factors that are known to regulate chondrocyte maturation and differentiation. Using promoter-reporter assays and mRNA analysis we have analyzed the role of chondrocyte-expressed transcription factors NFATp and Runx2 and have shown that ADAMTS-4 is a potential downstream target of these two factors. Our results suggest that inhibition of the expression/function of NFATp and/or Runx2 may enable us to modulate aggrecan degradation in normal physiology and/or in degenerative joint diseases. The ADAMTS-4 promoter would serve as a valuable mechanistic tool to better understand the regulation of ADAMTS-4 expression by signaling pathways that modulate cartilage matrix breakdown.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Procolágeno N-Endopeptidasa
/
Factores de Transcripción
/
Activación Transcripcional
/
Citocinas
/
Proteínas ADAM
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos