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http://purl.uniprot.org/citations/20862685http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20862685http://www.w3.org/2000/01/rdf-schema#comment"

Objective

To investigate the role of histone H3 lysine 4 (H3K4) methylation in interleukin-1β (IL-1β)-induced cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in human osteoarthritic (OA) chondrocytes.

Methods

Chondrocytes were stimulated with IL-1, and the expression of iNOS and COX-2 messenger RNA and proteins was evaluated by real-time reverse transcriptase-polymerase chain reaction analysis and Western blotting, respectively. H3K4 methylation and the recruitment of the histone methyltransferases SET-1A and MLL-1 to the iNOS and COX-2 promoters were evaluated using chromatin immunoprecipitation assays. The role of SET-1A was further evaluated using the methyltransferase inhibitor 5'-deoxy-5'-(methylthio)adenosine (MTA) and gene silencing experiments. SET-1A level in cartilage was determined using immunohistochemistry.

Results

The induction of iNOS and COX-2 expression by IL-1 was associated with H3K4 di- and trimethylation at the iNOS and COX-2 promoters. These changes were temporally correlated with the recruitment of the histone methyltransferase SET-1A, suggesting an implication of SET-1A in these modifications. Treatment with MTA inhibited IL-1-induced H3K4 methylation as well as IL-1-induced iNOS and COX-2 expression. Similarly, SET-1A gene silencing with small interfering RNA prevented IL-1-induced H3K4 methylation at the iNOS and COX-2 promoters as well as iNOS and COX-2 expression. Finally, we showed that the level of SET-1A expression was elevated in OA cartilage as compared with normal cartilage.

Conclusion

These results indicate that H3K4 methylation by SET-1A contributes to IL-1-induced iNOS and COX-2 expression and suggest that this pathway could be a potential target for pharmacologic intervention in the treatment of OA and possibly other arthritic diseases."xsd:string
http://purl.uniprot.org/citations/20862685http://purl.org/dc/terms/identifier"doi:10.1002/art.27762"xsd:string
http://purl.uniprot.org/citations/20862685http://purl.uniprot.org/core/author"Kapoor M."xsd:string
http://purl.uniprot.org/citations/20862685http://purl.uniprot.org/core/author"Duval N."xsd:string
http://purl.uniprot.org/citations/20862685http://purl.uniprot.org/core/author"Chabane N."xsd:string
http://purl.uniprot.org/citations/20862685http://purl.uniprot.org/core/author"Zayed N."xsd:string
http://purl.uniprot.org/citations/20862685http://purl.uniprot.org/core/author"Fahmi H."xsd:string
http://purl.uniprot.org/citations/20862685http://purl.uniprot.org/core/author"Martel-Pelletier J."xsd:string
http://purl.uniprot.org/citations/20862685http://purl.uniprot.org/core/author"Pelletier J.P."xsd:string
http://purl.uniprot.org/citations/20862685http://purl.uniprot.org/core/author"Benderdour M."xsd:string
http://purl.uniprot.org/citations/20862685http://purl.uniprot.org/core/author"El Mansouri F.E."xsd:string
http://purl.uniprot.org/citations/20862685http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/20862685http://purl.uniprot.org/core/name"Arthritis Rheum"xsd:string
http://purl.uniprot.org/citations/20862685http://purl.uniprot.org/core/pages"168-179"xsd:string
http://purl.uniprot.org/citations/20862685http://purl.uniprot.org/core/title"Contribution of H3K4 methylation by SET-1A to interleukin-1-induced cyclooxygenase 2 and inducible nitric oxide synthase expression in human osteoarthritis chondrocytes."xsd:string
http://purl.uniprot.org/citations/20862685http://purl.uniprot.org/core/volume"63"xsd:string
http://purl.uniprot.org/citations/20862685http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/20862685
http://purl.uniprot.org/citations/20862685http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/20862685
http://purl.uniprot.org/uniprot/O15047#attribution-4891ED7B3C2F5755F4965ABC7DB25DF0http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/20862685