http://purl.uniprot.org/citations/22065068 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/22065068 | http://www.w3.org/2000/01/rdf-schema#comment | "Proinflammatory cytokines such as interleukin-1 beta (IL-1β) stimulate cartilage extracellular matrix aggrecan degradation by aggrecanases or ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) during the pathogenesis of arthritis. Human aggrecanase-1 (ADAMTS-4) gene promoter contains at least one specificity protein-1 (Sp1)-transcription factor-binding site. We investigated the previously unknown role of Sp1 in the regulation of ADAMTS-4 gene expression in human articular chondrocytes. Mithramycin and WP631, the specific inhibitors of guanine cytosine (GC)-rich Sp1 DNA binding, partially suppressed IL-1-induced ADAMTS-4 expression and activity. Genetic inhibition of Sp1 by antisense oligonucleotide or by small interfering RNA (siRNA)-mediated Sp1 knockdown partially inhibited ADAMTS-4 induction by IL-1. Sense oligonucleotide and negative control siRNA had no effect. In contrast, cytomegalovirus promoter-driven Sp1 overexpression further enhanced IL-1-induced ADAMTS-4 expression and activity. Constitutively expressed glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was not affected by any of the agents. These results provide pharmacological and genetic evidence for the importance of Sp1 in ADAMTS-4 gene regulation by IL-1. Thus, Sp1 could be potentially targeted to reduce arthritis-associated cartilage aggrecan loss."xsd:string |
http://purl.uniprot.org/citations/22065068 | http://purl.org/dc/terms/identifier | "doi:10.1007/s00296-011-2187-1"xsd:string |
http://purl.uniprot.org/citations/22065068 | http://purl.uniprot.org/core/author | "Ahmad R."xsd:string |
http://purl.uniprot.org/citations/22065068 | http://purl.uniprot.org/core/author | "Zafarullah M."xsd:string |
http://purl.uniprot.org/citations/22065068 | http://purl.uniprot.org/core/author | "Sylvester J."xsd:string |
http://purl.uniprot.org/citations/22065068 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
http://purl.uniprot.org/citations/22065068 | http://purl.uniprot.org/core/name | "Rheumatol Int"xsd:string |
http://purl.uniprot.org/citations/22065068 | http://purl.uniprot.org/core/pages | "517-522"xsd:string |
http://purl.uniprot.org/citations/22065068 | http://purl.uniprot.org/core/title | "Role of Sp1 transcription factor in Interleukin-1-induced ADAMTS-4 (aggrecanase-1) gene expression in human articular chondrocytes."xsd:string |
http://purl.uniprot.org/citations/22065068 | http://purl.uniprot.org/core/volume | "33"xsd:string |
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