Modulation of the long non-coding RNA Mir155hg by high, but not moderate, hydrostatic pressure in cartilage precursor cells.
Modulation of the long non-coding RNA Mir155hg by high, but not moderate, hydrostatic pressure in cartilage precursor cells.
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DOI：
10.1371/journal.pone.0275682
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
Ushida, Takashi
中科院分区：
文献类型：
--
作者：
Montagne, Kevin;Furukawa, Katsuko S.;Taninaka, Yuki;Ngao, Brandon;Ushida, Takashi
骨关节炎（OA）是老年人最常见的关节疾病，其特征是由于软骨基质基因表达减少和参与蛋白质降解、细胞凋亡和炎症的基因表达增加而导致关节软骨逐渐退化。由于软骨的高含水量，软骨细胞感受到的主要物理刺激之一是静水压力。我们之前的研究表明，高于20mpa的高压诱导软骨前体细胞的基因表达变化与OA中观察到的相似。微rna是一种小的非编码rna，对包括OA在内的许多生理和病理过程至关重要。由于发现微rna miR-155在OA软骨细胞中升高，我们研究了高压对miR-155宿主基因Mir155hg表达的影响。将软骨细胞祖细胞系ATDC5置于25 MPa静水压力下加压，检测Mir155hg或由此产生的微rna的表达；使用药物抑制剂来确定参与调节Mir155hg的信号通路。我们发现，在软骨细胞祖细胞中，Mir155hg在高而非中等压力下会被强烈而迅速地上调。这种上调可能涉及膜通道pannexin-1和几个细胞内信号分子，包括PKC和Src。MiR-155-5p和-3p也受到压力的上调，但上调时间略晚于Mir155hg，并且已知的一组MiR-155-5p靶基因，包括Ikbke、Smarca4和Ywhae，都受到压力的影响，这表明Mir155hg可能在软骨生理中起重要作用。
Osteoarthritis (OA) is the most common joint disease in older adults and is characterized by a gradual degradation of articular cartilage due to decreased cartilage matrix gene expression and increased expression of genes involved in protein degradation, apoptosis and inflammation. Due to the high water content of cartilage, one of the main physical stimuli sensed by chondrocytes is hydrostatic pressure. We previously showed that high pressure above 20 MPa induced gene expression changes in chondrocyte precursor cells similar to what is observed in OA. Micro-RNAs are small non-coding RNAs essential to many physiological and pathological process including OA. As the micro-RNA miR-155 has been found increased in OA chondrocytes, we investigated the effects of high pressure on the expression of the miR-155 host gene Mir155hg. The chondrocyte progenitor cell line ATDC5 was pressurized under hydrostatic pressure up to 25 MPa and the expression of Mir155hg or the resulting micro-RNAs were measured; pharmacological inhibitors were used to identify the signaling pathways involved in the regulation of Mir155hg. We found that Mir155hg is strongly and rapidly up-regulated by high, but not moderate, pressure in chondrocyte progenitor cells. This up-regulation likely involves the membrane channel pannexin-1 and several intracellular signaling molecules including PKC and Src. MiR-155-5p and -3p were also up-regulated by pressure though somewhat later than Mir155hg, and a set of known miR-155-5p target genes, including Ikbke, Smarca4 and Ywhae, was affected by pressure, suggesting that Mir155hg may have important roles in cartilage physiology.
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