CCN2 as a Novel Molecule Supporting Energy Metabolism of Chondrocytes. Issue 5 (May 2014)

• Record Type: Journal Article
• Authors: Maeda‐Uematsu, Aya; Kubota, Satoshi; Kawaki, Harumi; Kawata, Kazumi; Miyake, Yoshiaki; Hattori, Takako; Nishida, Takashi; Moritani, Norifumi; Lyons, Karen M.; Iida, Seiji; Takigawa, Masaharu
• Is Part Of: Journal of cellular biochemistry. Volume 115:Issue 5(2014:May)
• Page Start: 854
• Page End: 865
• Publication Date: 2014-05
• Subjects: Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.24728
• Languages: English
• ISSNs: 0730-2312

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>ABSTRACT</title> <sec id="jcb24728-sec-0001" sec-type="section"> <p>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 <italic>Ccn2</italic>‐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 <italic>Ccn2</italic>‐null chondrocytes. The addition of recombinant CCN2 (rCCN2) to cultured <italic>Ccn2</italic>‐null chondrocytes partly redeemed the cellular ATP level attenuated by <italic>Ccn2</italic> deletion. Next, in order to investigate the mechanistic background that mediates the reduction in ATP level in these <italic>Ccn2</italic>‐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 <italic>Ccn2</italic> deletion, whereas a few genes required for aerobic and anaerobic ATP production were down‐regulated in the <italic>Ccn2</italic>‐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. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>