Expression and function of CCN2-derived circRNAs in chondrocytes.

IF 3.6 3区生物学 Q3 CELL BIOLOGY

Journal of Cell Communication and Signaling Pub Date : 2023-12-01 Epub Date: 2023-09-11 DOI:10.1007/s12079-023-00782-7

Soma Kato, Kazumi Kawata, Takashi Nishida, Tomomi Mizukawa, Masaharu Takigawa, Seiji Iida, Satoshi Kubota

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Abstract

Cellular communication network factor 2 (CCN2) molecules promote endochondral ossification and articular cartilage regeneration, and circular RNAs (circRNAs), which arise from various genes and regulate gene expression by adsorbing miRNAs, are known to be synthesized from CCN2 in human vascular endothelial cells and other types of cells. However, in chondrocytes, not only the function but also the presence of CCN2-derived circRNA remains completely unknown. In the present study, we investigated the expression and function of CCN2-derived circRNAs in chondrocytes. Amplicons smaller than those from known CCN2-derived circRNAs were observed using RT-PCR analysis that could specifically amplify CCN2-derived circRNAs in human chondrocytic HCS-2/8 cells. The nucleotide sequences of the PCR products indicated novel circRNAs in the HCS-2/8 cells that were different from known CCN2-derived circRNAs. Moreover, the expression of several Ccn2-derived circRNAs in murine chondroblastic ATDC5 cells was confirmed and observed to change alongside chondrocytic differentiation. Next, one of these circRNAs was knocked down in HCS-2/8 cells to investigate the function of the human CCN2-derived circRNA. As a result, CCN2-derived circRNA knockdown significantly reduced the expression of aggrecan mRNA and proteoglycan synthesis. Our data suggest that CCN2-derived circRNAs are expressed in chondrocytes and play a role in chondrogenic differentiation. Production and role of CCN2-derived RNAs in chondrocytes.

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源自 CCN2 的 circRNA 在软骨细胞中的表达和功能

细胞通讯网络因子 2（CCN2）分子可促进软骨内骨化和关节软骨再生，而在人类血管内皮细胞和其他类型的细胞中，由 CCN2 合成的环状 RNA（circRNA）可产生于各种基因，并通过吸附 miRNA 来调节基因表达。然而，在软骨细胞中，CCN2衍生的circRNA不仅功能未知，其存在也完全未知。在本研究中，我们调查了CCN2衍生的circRNA在软骨细胞中的表达和功能。通过 RT-PCR 分析，我们观察到了比已知的 CCN2 衍生 circRNA 更小的扩增子，可以特异性地扩增人软骨细胞 HCS-2/8 细胞中的 CCN2 衍生 circRNA。PCR 产物的核苷酸序列表明，HCS-2/8 细胞中的新型 circRNA 与已知的 CCN2 衍生 circRNA 不同。此外，在小鼠软骨母细胞 ATDC5 细胞中，几种 Ccn2 衍生的 circRNA 的表达得到了证实，并观察到它们随着软骨母细胞的分化而变化。接下来，在 HCS-2/8 细胞中敲除了其中一个 circRNA，以研究人 CCN2 衍生 circRNA 的功能。结果发现，CCN2衍生的circRNA被敲除后，凝集素mRNA的表达和蛋白多糖的合成明显减少。我们的数据表明，CCN2衍生的circRNA在软骨细胞中表达，并在软骨分化中发挥作用。CCN2衍生RNA在软骨细胞中的产生和作用。

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来源期刊

Journal of Cell Communication and Signaling CELL BIOLOGY-

CiteScore

6.40

自引率

4.90%

发文量

期刊介绍： The Journal of Cell Communication and Signaling provides a forum for fundamental and translational research. In particular, it publishes papers discussing intercellular and intracellular signaling pathways that are particularly important to understand how cells interact with each other and with the surrounding environment, and how cellular behavior contributes to pathological states. JCCS encourages the submission of research manuscripts, timely reviews and short commentaries discussing recent publications, key developments and controversies. Research manuscripts can be published under two different sections : In the Pathology and Translational Research Section (Section Editor Andrew Leask) , manuscripts report original research dealing with celllular aspects of normal and pathological signaling and communication, with a particular interest in translational research. In the Molecular Signaling Section (Section Editor Satoshi Kubota) manuscripts report original signaling research performed at molecular levels with a particular interest in the functions of intracellular and membrane components involved in cell signaling.