CCN2 as a novel molecule supporting energy metabolism of chondrocytes.
CCN2 as a novel molecule supporting energy metabolism of chondrocytes.
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DOI：
10.1002/jcb.24728
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发表时间：
2014-05
影响因子：
4
通讯作者：
Takigawa, Masaharu
中科院分区：
文献类型：
--
作者：
Maeda-Uematsu, Aya;Kubota, Satoshi;Kawaki, Harumi;Kawata, Kazumi;Miyake, Yoshiaki;Hattori, Takako;Nishida, Takashi;Moritani, Norifumi;Lyons, Karen M.;Iida, Seiji;Takigawa, Masaharu
CCN 2/结缔组织生长因子（CTGF）是一种独特的分子，其通过与许多细胞外生物分子的基质细胞相互作用促进软骨细胞分化和增殖。CCN 2的这种明显矛盾的功能特性表明其在基本细胞活动中的某些作用，例如增殖和分化所需的能量代谢。从野生型和Ccn 2-null小鼠分离的肋软骨细胞的比较代谢组学分析显示，后者的整体代谢受损。在分析的众多代谢物中，观察到细胞内ATP、GTP、CTP或UTP水平的稳定降低，表明CCN 2在能量代谢中的重要作用。特别地，在Ccn 2缺失的软骨细胞中，ATP的细胞水平降低超过50%。加入重组CCN 2（rCCN 2）培养CCN 2空软骨细胞部分赎回CCN 2缺失衰减的细胞ATP水平。接下来，为了研究介导这些Ccn 2缺失软骨细胞中ATP水平降低的机制背景，我们进行了转录组分析。结果发现，几个代谢相关基因在突变小鼠中表达上调或下调。在Ccn 2缺失的软骨细胞中，观察到一些核糖体蛋白基因的上调，而一些需氧和无氧ATP产生所需的基因在Ccn 2缺失的软骨细胞中下调。在这些基因中，烯醇化酶1基因表达的减少特别值得注意。这些发现揭示了CCN 2在生长板软骨细胞中作为代谢支持者的新功能作用，这是哺乳动物骨骼发生所需的。
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 fewgenes 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.
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影响因子：
6.2
作者：
Kawaki, Harumi;Kubota, Satoshi;Takigawa, Masaharu
通讯作者：
Takigawa, Masaharu
影响因子：
6.2
作者：
Nishida, T;Kubota, S;Takigawa, M
通讯作者：
Takigawa, M
影响因子：
4.6
作者：
Ivkovic, S;Yoon, BS;Lyons, KM
通讯作者：
Lyons, KM
影响因子：
4.1
作者：
Kubota, Satoshi;Takigawa, Masaharu
通讯作者：
Takigawa, Masaharu
影响因子：
4.8
作者：
Nakanishi, T;Nishida, T;Takigawa, M
通讯作者：
Takigawa, M