Regulation of chicken ccn2 gene by interaction between RNA cis-element and putative trans-factor during differentiation of chondrocytes

Yoshiki Mukudai, Satoshi Kubota, Takanori Eguchi, Seiji Kondo, Kyouji Nakao, Masaharu Takigawa

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23 Citations (Scopus)

Abstract

CCN2/CTGF is a multifunctional growth factor. Our previous studies have revealed that CCN2 plays important roles in both growth and differentiation of chondrocytes and that the 3′-untranslated region (3′-UTR) of ccn2 mRNA contains a cis-repressive element of gene expression. In the present study, we found that the stability of chicken ccn2 mRNA is regulated in a differentiation stage-dependent manner in chondrocytes. We also found that stimulation by bone morphogenetic protein 2, platelet-derived growth factor, and CCN2 stabilized ccn2 mRNA in proliferating chondrocytes but that it destabilized the mRNA in prehypertrophic-hypertrophic chondrocytes. The results of a reporter gene assay revealed that the minimal repressive cis-element of the 3′-UTK of chicken ccn2 mRNA was located within the area between 100 and 150 bases from the polyadenylation tail. Moreover, the stability of ccn2 mRNA was correlated with the interaction between this cis-element and a putative 40-kDa trans-factor in nuclei and cytoplasm. In fact, the binding between them was prominent in proliferating chondrocytes and attenuated in (pre)hypertrophic chondrocytes. Stimulation by the growth factors repressed the binding in proliferating chondrocytes; however, it enhanced it in (pre)hypertrophic chondrocytes. Therefore, gene expression of ccn2 mRNA during endochondral ossification is properly regulated, at least in part, by changing the stability of the mRNA, which arises from the interaction between the RNA cis-element and putative trans-factor.

Original languageEnglish
Pages (from-to)3166-3177
Number of pages12
JournalJournal of Biological Chemistry
Volume280
Issue number5
DOIs
Publication statusPublished - Feb 4 2005

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Chondrocytes
Chickens
Genes
RNA
Messenger RNA
RNA Stability
Gene expression
Intercellular Signaling Peptides and Proteins
Gene Expression
Bone Morphogenetic Protein 2
Polyadenylation
Platelet-Derived Growth Factor
3' Untranslated Regions
Reporter Genes
Osteogenesis
Tail
Assays
Cytoplasm
Growth

ASJC Scopus subject areas

  • Biochemistry

Cite this

Regulation of chicken ccn2 gene by interaction between RNA cis-element and putative trans-factor during differentiation of chondrocytes. / Mukudai, Yoshiki; Kubota, Satoshi; Eguchi, Takanori; Kondo, Seiji; Nakao, Kyouji; Takigawa, Masaharu.

In: Journal of Biological Chemistry, Vol. 280, No. 5, 04.02.2005, p. 3166-3177.

Research output: Contribution to journalArticle

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