Table_4_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待充分研究的细胞间通讯途径。我们假设，在实验性骨关节炎的发展过程中，关节滑液和血浆中的小非编码RNA表达模式将会发生改变。在本研究中，我们首次对血浆和关节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小RNA测序，以提供一个关于马创伤性骨关节炎后模型中细胞外囊泡携带的小非编码RNA的全面概述。此外，我们还对关节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。血浆和关节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）及四种核糖核酸（U3、snord15、snord46和snord58）的不同时序表达，代表着早期骨关节炎的潜在生物标志物。对关节滑液中差异表达微RNA的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，同时增加了干细胞的存活和分化。血浆和关节滑液来源的细胞外囊泡小非编码RNA特征首次在骨关节炎的时序模型中建立。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。