Multi-pathway Protective Effects of MicroRNAs on Human Chondrocytes in an In Vitro Model of Osteoarthritis
Multi-pathway Protective Effects of MicroRNAs on Human Chondrocytes in an In Vitro Model of Osteoarthritis
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DOI：
10.1016/j.omtn.2019.07.011
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发表时间：
2019-09-06
影响因子：
8.8
通讯作者：
Karlsen, Tommy A.
中科院分区：
文献类型：
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作者：
Al-Modawi, Rua Nader;Brinchmann, Jan E.;Karlsen, Tommy A.
y骨关节炎（OA）是最常见的退行性关节疾病。OA的主要致病因素之一被认为是炎症。与OA相关的其他因素是microRNA的失调、自噬活性降低、氧化应激和代谢改变。microRNA是小的非编码RNA，是基因表达的强大调节因子。miR-140- 5 p被认为是软骨特异性microRNA，是体外软骨形成所必需的，具有抗炎特性，并且在骨关节炎软骨中下调。其乘客链miR-140- 3 p是健康软骨中表达最高的microRNA，并在体外软骨形成过程中增加。miR-146 a是一种众所周知的抗炎微小RNA。一些研究已经阐明了它在OA和自身免疫性疾病中的作用。我们发现，当人软骨细胞分别转染miR-140- 5 p，miR-140- 3 p，或miR-146 a，然后用白细胞介素-1 β和肿瘤因子坏死-α刺激作为OA的炎症模型时，这些microRNA中的每一种都表现出相似的保护作用。质谱分析提供了对改变的蛋白质组的深入了解。所有三种microRNA都下调了重要的炎症介质。此外，它们影响属于相同生物过程的不同蛋白质，表明炎症和氧化应激的整体抑制，自噬的增强和其他稳态细胞机制的恢复，包括代谢。
y Osteoarthritis (OA) is the most common degenerative joint disease. One of the main pathogenic factors of OA is thought to be inflammation. Other factors associated with OA are dys-regulation of microRNAs, reduced autophagic activity, oxidative stress, and altered metabolism. microRNAs are small non-coding RNAs that are powerful regulators of gene expression. miR-140-5p is considered a cartilage-specific microRNA, is necessary for in vitro chondrogenesis, has anti-inflammatory properties, and is downregulated in osteoarthritic cartilage. Its passenger strand, miR-140-3p, is the most highly expressed microRNA in healthy cartilage and increases during in vitro chondrogenesis. miR-146a is a well-known anti-inflammatory microRNA. Several studies have illustrated its role in OA and autoimmune diseases. We show that, when human chondrocytes were transfected individually with miR-140-5p, miR-140-3p, or miR-146a prior to stimulation with interleukin-1 beta and tumor factor necrosis-alpha as an inflammatory model of OA, each of these microRNAs exhibited similar protective effects. Mass spectrometry analysis provided an insight to the altered proteome. All three microRNAs downregulated important inflammatory mediators. In addition, they affected different proteins belonging to the same biological processes, suggesting an overall inhibition of inflammation and oxidative stress, enhancement of autophagy, and restoration of other homeostatic cellular mechanisms, including metabolism.