Regulation of human COL2A1 gene expression in chondrocytes: Identification of C-Krox-responsive elements and modulation by phenotype alteration

Chafik Ghayor, Jean François Herrouin, Christos Chadjichristos, Leena Ala-Kokko, Masaharu Takigawa, Jean Pierre Pujol, Philippe Galéra

Research output: Contribution to journalArticlepeer-review

69 Citations (Scopus)

Abstract

To identify control motifs involved in human type II collagen gene transcription in both differentiated and dedifferentiated rabbit articular chondrocytes, transient transfection experiments were performed. A 715-base pair (bp) region of the first intron (+2127/+2842), including a 153-bp sequence so far uncharacterized (+2689/+2842), was found to mediate enhancer activity. In dedifferentiated chondrocytes, this enhancer activity was shown to be less effective than in primary cultures but still present. We then demonstrated that a zinc finger protein, C-Krox, activates COL2A1 gene transcription in differentiated chondrocytes through the enhancer region, whereas in subcultured cells, it inhibited the gene activity via a 266-bp promoter. Multicopies of the C-Krox binding site were found to mediate transactivation in both primary cultures and passaged cells, whereas C-Krox overexpression inhibited transcription in dedifferentiated chondrocytes. Additionally, we showed that C-Krox binds to several cis sequences that mediate its transcriptional effects. During chondrocyte dedifferentiation, the protein levels and binding activity of C-Krox were reduced, whereas those of NF-κB were increased. This was not associated with variations of mRNA levels, suggesting that post-transcriptional regulatory mechanisms could be involved in C-Krox expression. These results suggest that C-Krox plays a major role in type II collagen expression and the chondrocyte phenotype modulation.

Original languageEnglish
Pages (from-to)27421-27438
Number of pages18
JournalJournal of Biological Chemistry
Volume275
Issue number35
DOIs
Publication statusPublished - Sep 1 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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