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Mol. Cell. Biol. doi:10.1128/MCB.00495-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Post-transcriptional regulation of chicken ccn2 gene expression by nucleophosmin/B23 during chondrocyte differentiation

Biodental Research Center, Okayama University Dental School, and Department of Biochemistry and Molecular Dentistry, and Department of Oral and Maxillofacial Surgery and Biopathological Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8525, Japan

^* To whom correspondence should be addressed. Email: takigawa{at}md.okayama-u.ac.jp.

	Abstract

CCN2/CTGF is a multifunctional factor that plays a crucial role in the growth and differentiation of chondrocytes. The chicken ccn2 gene is regulated not only at the transcriptional level, but also by the interaction between a post-transcriptional element in the 3'-untranslated region (3'-UTR) and a cofactor. In the present study, we identified a nucleophosmin (NPM/B23) as this cofactor. Binding of NPM to the element was confirmed, and subsequent analysis revealed a significant correlation between the decrease in cytosolic NPM and the increased stability of the ccn2 mRNA during chondrocyte differentiation in vivo. Furthermore, recombinant chicken NPM enhanced the degradation of chimeric RNAs containing the post-transcriptional cis-elements in a chicken embryonic fibroblast extract in vitro. Of note, RNA destabilization effect by NPM was far more prominent in the cytosolic extract of chondrocytes than in that of the fibroblasts, representing a chondrocyte-specific action of NPM. Stimulation by growth factors to promote differentiation changed the subcellular distribution of NPM in chondrocytes, which followed the expected patterns from the resultant change in the ccn2 mRNA stability. Therefore, the present study reveals a novel aspect of NPM as a key player in the post-transcriptional regulation of ccn2 mRNA during the differentiation of chondrocytes.