Liu Huachen, Yan Lei, Li Xiaoke, Li Dijun, Wang Guishan, Shen Nan-Nan, Li Jiao Jiao, Wang Bin
Department of Orthopaedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Qingchun Road No. 79, Hangzhou, China.
Shanxi Medical University, Taiyuan, China.
Clin Exp Med. 2023 Nov;23(7):3737-3749. doi: 10.1007/s10238-023-01063-8. Epub 2023 Apr 7.
Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases globally, leading to chronic disability and poor prognosis. One of the approaches for optimizing OA treatment is to find early effective diagnostic biomarkers. The contribution of microRNAs (miRNAs) in OA progression is now being increasingly recognized. This review provides a comprehensive summary on studies reporting the expression profiling of miRNAs in OA and associated signaling pathways. We performed a systematic search of the Embase, Web of Science, PubMed, and Cochrane library databases. This systematic review is reported according to the PRISMA checklist. Studies which identified miRNAs with aberrant expression compared to controls during OA progression were included, and a meta-analysis was performed. Results from the random effects model were provided as log10 odds ratios (logORs) and 95% confidence intervals. Sensitivity analysis was conducted to confirm the accuracy of the results. Subgroup analysis was conducted based on tissue source. The target genes of miRNAs identified in this study were extracted from the MiRWalk database, and these target genes were enriched in Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. A total of 191 studies reporting 162 miRNAs were included in our meta-analysis. Among them, 36 miRNAs distributed across 96 studies were expressed in the same direction in at least two studies (13 up-regulated and 23 down-regulated). Subgroup analysis of tissue source revealed that the highest number of studies was conducted using articular cartilage, where the most up-regulated miRNAs were miR-146a-5p (logOR 7.355; P < 0.001) and miR-34a-5p (logOR 6.955; P < 0.001), and the most down-regulated miRNAs were miR-127-5p (logOR 6.586; P < 0.001) and miR-140-5p (logOR 6.373; P < 0.001). Enrichment analysis of 752 downstream target genes of all identified miRNAs was performed, and the regulatory relationships among them were displayed. Mesenchymal stem cells and transforming growth factor-β were found to be the most important downstream effectors regulated by miRNA in OA. This study highlighted the importance of miRNA signaling in OA progression and identified a number of prominent miRNAs including miR-146a-5p, miR-34a-5p, miR-127-5p, and miR-140-5p which might be considered as potential biomarkers for OA.
骨关节炎（OA）是全球最常见的肌肉骨骼疾病之一，会导致慢性残疾和预后不良。优化OA治疗的方法之一是寻找早期有效的诊断生物标志物。微小RNA（miRNA）在OA进展中的作用现在越来越受到认可。本综述全面总结了报道miRNA在OA中的表达谱及相关信号通路的研究。我们对Embase、Web of Science、PubMed和Cochrane图书馆数据库进行了系统检索。本系统综述按照PRISMA清单报告。纳入了在OA进展过程中与对照组相比鉴定出miRNA表达异常的研究，并进行了荟萃分析。随机效应模型的结果以log10优势比（logOR）和95%置信区间表示。进行敏感性分析以确认结果的准确性。基于组织来源进行亚组分析。本研究中鉴定出的miRNA的靶基因从MiRWalk数据库中提取，这些靶基因在基因本体论和京都基因与基因组百科全书通路中富集。我们的荟萃分析共纳入了191项报告162种miRNA的研究。其中，分布在96项研究中的36种miRNA在至少两项研究中表达方向相同（13种上调，23种下调）。组织来源的亚组分析显示，使用关节软骨进行的研究数量最多，其中上调最多的miRNA是miR-146a-5p（logOR 7.355；P＜0.001）和miR-34a-5p（logOR 6.955；P＜0.001），下调最多的miRNA是miR-127-5p（logOR 6.586；P＜0.001）和miR-140-5p（logOR 6.373；P＜0.001）。对所有鉴定出的miRNA的752个下游靶基因进行了富集分析，并展示了它们之间的调控关系。发现间充质干细胞和转化生长因子-β是OA中受miRNA调控的最重要的下游效应物。本研究强调了miRNA信号在OA进展中的重要性，并鉴定出了一些突出的miRNA，包括miR-146a-5p、miR-34a-5p、miR-127-5p和miR-140-5p，它们可能被视为OA的潜在生物标志物。
