論文

査読有り
2014年5月

CCN2 as a Novel Molecule Supporting Energy Metabolism of Chondrocytes

JOURNAL OF CELLULAR BIOCHEMISTRY
  • Aya Maeda-Uematsu
  • ,
  • Satoshi Kubota
  • ,
  • Harumi Kawaki
  • ,
  • Kazumi Kawata
  • ,
  • Yoshiaki Miyake
  • ,
  • Takako Hattori
  • ,
  • Takashi Nishida
  • ,
  • Norifumi Moritani
  • ,
  • Karen M. Lyons
  • ,
  • Seiji Iida
  • ,
  • Masaharu Takigawa

115
5
開始ページ
854
終了ページ
865
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/jcb.24728
出版者・発行元
WILEY-BLACKWELL

CCN2/connective tissue growth factor (CTGF) is a unique molecule that promotes both chondrocytic differentiation and proliferation through its matricellular interaction with a number of extracellular biomolecules. This apparently contradictory functional property of CCN2 suggests its certain role in basic cellular activities such as energy metabolism, which is required for both proliferation and differentiation. Comparative metabolomic analysis of costal chondrocytes isolated from wild-type and Ccn2-null mice revealed overall impaired metabolism in the latter. Among the numerous metabolites analyzed, stable reduction in the intracellular level of ATP, GTP, CTP, or UTP was observed, indicating a profound role of CCN2 in energy metabolism. Particularly, the cellular level of ATP was decreased by more than 50% in the Ccn2-null chondrocytes. The addition of recombinant CCN2 (rCCN2) to cultured Ccn2-null chondrocytes partly redeemed the cellular ATP level attenuated by Ccn2 deletion. Next, in order to investigate the mechanistic background that mediates the reduction in ATP level in these Ccn2-null chondrocytes, we performed transcriptome analysis. As a result, several metabolism-associated genes were found to have been up-regulated or down-regulated in the mutant mice. Up-regulation of a number of ribosomal protein genes was observed upon Ccn2 deletion, whereas a few genes required for aerobic and anaerobic ATP production were down-regulated in the Ccn2-null chondrocytes. Among such genes, reduction in the expression of the enolase 1 gene was of particular note. These findings uncover a novel functional role of CCN2 as a metabolic supporter in the growth-plate chondrocytes, which is required for skeletogenesis in mammals. J. Cell. Biochem. 115: 854-865, 2014. (c) 2013 Wiley Periodicals, Inc.

Web of Science ® 被引用回数 : 12

リンク情報
DOI
https://doi.org/10.1002/jcb.24728
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/24288211
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000332340300007&DestApp=WOS_CPL

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