Table_3_Small non-coding RNA landscape of extracellular vesicles from a post-traumatic model of equine osteoarthritis.DOCX

Extracellular vesicles comprise an as yet inadequately investigated intercellular communication pathway in the field of early osteoarthritis. We hypothesised that the small non-coding RNA expression pattern in synovial fluid and plasma would change during progression of experimental osteoarthritis. In this study, we conducted small RNA sequencing to provide a comprehensive overview of the temporal expression profiles of small non-coding transcripts carried by extracellular vesicles derived from plasma and synovial fluid for the first time in a posttraumatic model of equine osteoarthritis. Additionally, we characterised synovial fluid and plasma-derived extracellular vesicles with respect to quantity, size, and surface markers. The different temporal expressions of seven microRNAs in plasma and synovial fluid-derived extracellular vesicles, eca-miR-451, eca-miR-25, eca-miR-215, eca-miR-92a, eca-miR-let-7c, eca-miR-486-5p, and eca-miR-23a, and four snoRNAs, U3, snord15, snord46, and snord58, represent potential biomarkers for early osteoarthritis. Bioinformatics analysis of the differentially expressed microRNAs in synovial fluid highlighted that in early osteoarthritis these related to the inhibition of cell cycle, cell cycle progression, DNA damage and cell proliferation as well as increased cell viability and differentiation of stem cells. Plasma and synovial fluid-derived extracellular vesicle small non-coding signatures have been established for the first time in a temporal model of osteoarthritis. These could serve as novel biomarkers for evaluation of osteoarthritis progression or act as potential therapeutic targets.

细胞外囊泡构成了早期骨关节炎领域中尚未充分研究的一种细胞间通讯途径。我们假设，在实验性骨关节炎的发展过程中，滑液和血浆中的小非编码RNA表达模式将发生改变。在本研究中，我们首次通过小RNA测序，对血浆和滑液中提取的细胞外囊泡携带的小非编码转录本的时序表达谱进行了全面概述，这些细胞外囊泡是在马骨关节炎的创伤后模型中获得的。此外，我们还对滑液和血浆来源的细胞外囊泡在数量、大小和表面标志物方面进行了表征。血浆和滑液来源的细胞外囊泡中七种微RNA（eca-miR-451、eca-miR-25、eca-miR-215、eca-miR-92a、eca-miR-let-7c、eca-miR-486-5p和eca-miR-23a）以及四种核糖核酸（U3、snord15、snord46和snord58）的不同时序表达，代表了早期骨关节炎的潜在生物标志物。对滑液中差异表达的微RNA进行生物信息学分析表明，在早期骨关节炎中，这些微RNA与细胞周期抑制、细胞周期进程、DNA损伤和细胞增殖有关，以及干细胞存活率和分化的增加。首次在骨关节炎的时序模型中建立了血浆和滑液来源的细胞外囊泡小非编码特征，这些特征可作为评估骨关节炎进展的新生物标志物，或作为潜在的治疗靶点。