title: ADAMTS9 activation by interleukin 1 beta via NFATc1 in OUMS-27 chondrosarcoma cells and in human chondrocytes.
abstract: ADAMTS9 is a member of the disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) genes, with aggrecan-degrading activity. It has also been characterized to be reactive and highly activated ADAMTS by IL-1 beta in both chondrosarcoma cells and human chondrocytes (Demircan et al. Arthritis Rheum 52:1451-1460, 2005). In order to understand the regulation of ADAMTS9 gene expression a functional 3.0 kb human ADAMTS9 promoter has been cloned and characterized. A sequence analysis of the promoter revealed the presence of putative binding sites for Nuclear Factor of Activated T cells (NFAT), which is commonly found in the ADAMTS4 and ADAMTS5 promoters. NFATc1 was up-regulated in an activated form by IL-1 beta in human chondrocytes. The IL-1 beta inducible ADAMTS9 expression was inhibited by NFAT inhibitors, FK506 and 11Arg (11R)-VIVIT. Furthermore, direct binding of NFATc1 on distal and proximal promoters of ADAMTS9 was demonstrated by a chromatin immunoprecipitation assay. Promoter-reporter assays supported those results. These findings may provide a better understanding of the regulation of ADAMTS9 expression induced by inflammatory cytokines.
authors.affiliation: Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan.
authors.forename: Kursat Oguz
authors.initials: KO
authors.lastname: Yaykasli
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Oohashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirohata
authors.forename: Omer Faruk
authors.initials: OF
authors.lastname: Hatipoglu
authors.forename: Kiichi
authors.initials: K
authors.lastname: Inagawa
authors.forename: Kadir
authors.initials: K
authors.lastname: Demircan
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ninomiya
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000071119:ADAMTS9 Protein; D000818:Animals; D001483:Base Sequence; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D002813:Chondrosarcoma / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D051381:Rats
chemical_list: D053583:Interleukin-1beta; D050778:NFATC Transcription Factors; D020033:Protein Isoforms; D051722:ADAM Proteins; D000071119:ADAMTS9 Protein; C412869:ADAMTS9 protein, human