Regulatory mechanism of human connective tissue growth factor (CTGF/Hcs24) gene expression in a human chondrocytic cell line, HCS-2/8

Takanori Eguchi, Satoshi Kubota, Seiji Kondo, Tsuyoshi Shimo, Takako Hattori, Tohru Nakanishi, Takuo Kuboki, Hirofumi Yatani, Masaharu Takigawa

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

CTGF/Hcs24 is a multi-functional growth factor that potentiates either the growth or differentiation of mesenchymal cells, according to the biological conditions. Among various functional aspects of CTGF/Hcs24, it is especially notable that CTGF/Hcs24 may promote endochondral ossification in growth cartilage through all stages, and it is highly expressed in a human chondrosarcoma-derived chondrocytic cell line (HCS-2/8). In this study, to clarify the regulatory mechanism of CTGF/Hcs24 gene expression in chondrocytes, we analyzed the transcriptional activity of the CTGF/Hcs24 promoter and the effect of the CTGF/Hcs24 3′-untranslated region (3′-UTR) on gene expression in HCS-2/8 by means of an established DNA transfection and luciferase reporter gene assay system. As a result, the luciferase activity of the CTGF/Hcs24 promoter was found to be remarkably high in HCS-2/8. The 3′-UTR of the CTGF/Hcs24 gene strongly repressed the luciferase activity in HCS-2/8, when it was linked to the downstream of the luciferase reporter gene, suggesting its functionality also in chondrocytic cells. Deletion analysis of the CTGF/Hcs24 promoter clarified a major segment responsible for the enhanced CTGF/Hcs24 promoter activity in HCS-2/8. The TGF-β response element in the DNA segment was active in HCS-2/8, and point mutations in the element moderately decreased the highly maintained promoter activity with total loss of TGF-β responsiveness. These results indicate that the strong expression of the CTGF/Hcs24 gene in HCS-2/8 was mainly caused by high transcriptional activity of the CTGF/Hcs24 promoter, and that the TGF-β response element is one of the critical elements that support the high transcription activity.

Original languageEnglish
Pages (from-to)79-87
Number of pages9
JournalJournal of biochemistry
Volume130
Issue number1
DOIs
Publication statusPublished - Jan 1 2001

Keywords

  • CCN family
  • CTGF
  • Chondrocyte
  • HCS-2/8
  • Transcription

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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