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ID 52817
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Author
Maeda-Uematsu, Aya
Kawaki, Harumi
Kawata, Kazumi
Miyake, Yoshiaki
Moritani, Norifumi
Lyons, Karen M.
Takigawa, Masaharu
Abstract
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.
Keywords
CCN2
CTGF
CARTILAGE
CHONDROCYTES
METABOLISM
Published Date
2014-05
Publication Title
Journal of Cellular Biochemistry
Volume
volume115
Issue
issue5
Start Page
854
End Page
865
ISSN
0730-2312
Content Type
Journal Article
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/52552
language
英語
Copyright Holders
(c) 2013 Wiley Periodicals, Inc.
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