The Synovium Attenuates Cartilage Degeneration in KOA through Activation of the Smad2/3-Runx1 Cascade and Chondrogenesis-related miRNAs.
The Synovium Attenuates Cartilage Degeneration in KOA through Activation of the Smad2/3-Runx1 Cascade and Chondrogenesis-related miRNAs.
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滑膜通过激活 Smad2/3-Runx1 级联和软骨形成相关 miRNA 来减轻 KOA 软骨退化
DOI：
10.1016/j.omtn.2020.10.004
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发表时间：
2020-12-04
期刊：
影响因子：
--
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Zhao X;Meng F;Hu S;Yang Z;Huang H;Pang R;Wen X;Kang Y;Zhang Z
膝关节骨关节炎（KOA）是一种常见的老年人致残性关节疾病。进行性软骨退化是KOA的标志，但其更深层次的机制仍不清楚。大量证据表明滑膜对于关节内环境稳定的重要性。本研究旨在确定滑膜是否通过KOA微环境中的软骨形成相关microRNA（miRNAs）调节软骨代谢。临床样本测试和体外细胞实验筛选出miR-455和miR-210作为有效的miRNA。与对照组相比，两者的水平在KOA软骨中显著降低，但在KOA滑液中增加。我们进一步揭示了转化生长因子β1（TGF-β1）可以显著上调滑膜细胞中miR-455和miR-210的表达。上调的miRNA可以分泌到细胞外环境中并防止软骨退化。通过生物信息学和体外实验，我们发现Runx 1可以与miR-455和miR-210的启动子区结合，并在TGF-β1处理的滑膜细胞中增强其转录。总的来说，我们的研究结果证明了滑膜对软骨发生相关miRNA介导的软骨变性的保护作用，这表明Runx 1是KOA治疗的潜在靶点。老年人患严重的膝关节骨性关节炎。Zhang及其同事证明，膝骨关节炎滑液中TGF-β1刺激的滑膜细胞释放miR-455和miR-210可以预防软骨退化。整个过程受Smad 2/3-Runx 1级联反应的调控，揭示了Runx 1在KOA治疗中的潜在作用。
Knee osteoarthritis (KOA) is a highly prevalent disabling joint disease in aged people. Progressive cartilage degradation is the hallmark of KOA, but its deeper mechanism remains unclear. Substantial evidence indicates the importance of the synovium for joint homeostasis. The present study aimed to determine whether the synovium regulates cartilage metabolism through chondrogenesis-related microRNAs (miRNAs) in the KOA microenvironment. Clinical sample testing and in vitro cell experiments screened out miR-455 and miR-210 as effective miRNAs. The levels of both were significantly reduced in KOA cartilage but increased in KOA synovial fluid compared with controls. We further revealed that transforming growth factor β1 (TGF-β1) can significantly upregulate miR-455 and miR-210 expression in synoviocytes. The upregulated miRNAs can be secreted into the extracellular environment and prevent cartilage degeneration. Through bioinformatics and in vitro experiments, we found that Runx1 can bind to the promoter regions of miR-455 and miR-210 and enhance their transcription in TGF-β1-treated synoviocytes. Collectively, our findings demonstrate a protective effect of the synovium against cartilage degeneration mediated by chondrogenesis-related miRNAs, which suggests that Runx1 is a potential target for KOA therapy. Aged people suffer severely from knee osteoarthritis. Zhang and colleagues demonstrate that the release of miR-455 and miR-210 from TGF-β1-stimulated synoviocytes in knee osteoarthritis synovial fluid could prevent cartilage degeneration. The whole process was regulated by the Smad2/3-Runx1 cascade, which revealed the potential role of Runx1 in KOA therapy.
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