ADAMTS9 activation by interleukin 1β via NFATc1 in OUMS-27 chondrosarcoma cells and in human chondrocytes

Kursat Oguz Yaykasli, Toshitaka Oohashi, Satoshi Hirohata, Omer Faruk Hatipoglu, Kiichi Inagawa, Kadir Demircan, Yoshifumi Ninomiya

Research output: Contribution to journalArticle

39 Citations (Scopus)

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-1β 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-1β in human chondrocytes. The IL-1β 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.

Original languageEnglish
Pages (from-to)69-79
Number of pages11
JournalMolecular and Cellular Biochemistry
Volume323
Issue number1-2
DOIs
Publication statusPublished - 2009

Keywords

  • ADAMTS
  • Arthritis
  • Chondrocyte
  • NFAT
  • Protein transduction domain
  • VIVIT

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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