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

32 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

Fingerprint

Chondrosarcoma
Chondrocytes
Interleukin-1
NFATC Transcription Factors
Chemical activation
Assays
Rheum
Thrombospondins
Disintegrins
Aggrecans
Chromatin Immunoprecipitation
Gene Expression Regulation
Metalloproteases
Tacrolimus
Gene expression
Chromatin
Arthritis
Sequence Analysis
Genes
Binding Sites

Keywords

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

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

ADAMTS9 activation by interleukin 1β via NFATc1 in OUMS-27 chondrosarcoma cells and in human chondrocytes. / Yaykasli, Kursat Oguz; Oohashi, Toshitaka; Hirohata, Satoshi; Hatipoglu, Omer Faruk; Inagawa, Kiichi; Demircan, Kadir; Ninomiya, Yoshifumi.

In: Molecular and Cellular Biochemistry, Vol. 323, No. 1-2, 2009, p. 69-79.

Research output: Contribution to journalArticle

Yaykasli, Kursat Oguz ; Oohashi, Toshitaka ; Hirohata, Satoshi ; Hatipoglu, Omer Faruk ; Inagawa, Kiichi ; Demircan, Kadir ; Ninomiya, Yoshifumi. / ADAMTS9 activation by interleukin 1β via NFATc1 in OUMS-27 chondrosarcoma cells and in human chondrocytes. In: Molecular and Cellular Biochemistry. 2009 ; Vol. 323, No. 1-2. pp. 69-79.
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