Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis.

Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis.
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DOI:
10.1186/ar3013
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发表时间:
2010
影响因子:
4.9
通讯作者:
Nakamura T
Nakamura T
中科院分区:
医学2区
文献类型:
--
作者:
Murata K;Yoshitomi H;Tanida S;Ishikawa M;Nishitani K;Ito H;Nakamura T

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MicroRNA (miRNA) 是调节靶 mRNA 活性和细胞过程的内源性小非编码 RNA,以稳定形式存在于人血浆中。在这项研究中,我们研究了 miRNA 是否也稳定存在于滑液中,以及血浆和滑液 miRNA 是否可以作为类风湿性关节炎 (RA) 和骨关节炎 (OA) 的生物标志物。我们通过定量逆转录聚合酶链反应测量了 RA 和 OA 患者滑液中以及 RA、OA 和健康对照 (HC) 血浆中 miR-16、miR-132、miR-146a、miR-155 和 miR-223 的浓度。此外,还检查了滑膜组织、单层成纤维细胞样滑膜细胞和单核细胞的条件培养基中的miRNA。对 miRNA 和 RA 生物标志物或疾病活动之间的相关性进行了统计检查。滑液中存在 miRNA,并且与血浆 miRNA 一样稳定,可在 -20°C 下保存并在 -20°C 至 4°C 范围内冻融。在RA和OA中,滑液中miR-16、miR-132、miR-146a和miR-223的浓度显着低于其血浆浓度,并且血浆和滑液miRNA之间不存在相关性。有趣的是,滑膜组织、成纤维细胞样滑膜细胞和单核细胞以不同的模式分泌 miRNA。 OA滑液中miRNA的表达模式与滑膜组织分泌的miRNA相似。 RA 滑液 miRNA 可能源自滑膜组织和浸润细胞。 HC的血浆miR-132显着高于RA或OA,具有较高的诊断性。 RA滑液中miR-16、miR-146a、miR-155和miR-223浓度显着高于OA。血浆 miRNA 或滑液 miRNA 与血浆 miRNA 的比率(包括 miR-16 和 miR-146a)与压痛关节计数和 28 关节疾病活动评分显着相关。血浆 miRNA 与滑液 miRNA 具有不同的模式,滑液 miRNA 似乎源自滑液组织。血浆 miR-132 可以很好地区分 RA 或 OA 患者的 HC,而滑液 miRNA 可以区分 RA 和 OA。此外,血浆 miRNA 与 RA 的疾病活动相关。因此,滑液和血浆 miRNA 有潜力作为 RA 和 OA 的诊断生物标志物以及作为分析其发病机制的工具。
MicroRNAs (miRNAs), endogenous small noncoding RNAs regulating the activities of target mRNAs and cellular processes, are present in human plasma in a stable form. In this study, we investigated whether miRNAs are also stably present in synovial fluids and whether plasma and synovial fluid miRNAs could be biomarkers of rheumatoid arthritis (RA) and osteoarthritis (OA). We measured concentrations of miR-16, miR-132, miR-146a, miR-155 and miR-223 in synovial fluid from patients with RA and OA, and those in plasma from RA, OA and healthy controls (HCs) by quantitative reverse transcription-polymerase chain reaction. Furthermore, miRNAs in the conditioned medium of synovial tissues, monolayer fibroblast-like synoviocytes, and mononuclear cells were examined. Correlations between miRNAs and biomarkers or disease activities of RA were statistically examined. Synovial fluid miRNAs were present and as stable as plasma miRNAs for storage at -20°C and freeze-thawing from -20°C to 4°C. In RA and OA, synovial fluid concentrations of miR-16, miR-132, miR-146a, and miR-223 were significantly lower than their plasma concentrations, and there were no correlation between plasma and synovial fluid miRNAs. Interestingly, synovial tissues, fibroblast-like synoviocytes, and mononuclear cells secreted miRNAs in distinct patterns. The expression patterns of miRNAs in synovial fluid of OA were similar to miRNAs secreted by synovial tissues. Synovial fluid miRNAs of RA were likely to originate from synovial tissues and infiltrating cells. Plasma miR-132 of HC was significantly higher than that of RA or OA with high diagnosability. Synovial fluid concentrations of miR-16, miR-146a miR-155 and miR-223 of RA were significantly higher than those of OA. Plasma miRNAs or ratio of synovial fluid miRNAs to plasma miRNAs, including miR-16 and miR-146a, significantly correlated with tender joint counts and 28-joint Disease Activity Score. Plasma miRNAs had distinct patterns from synovial fluid miRNAs, which appeared to originate from synovial tissue. Plasma miR-132 well differentiated HCs from patients with RA or OA, while synovial fluid miRNAs differentiated RA and OA. Furthermore, plasma miRNAs correlated with the disease activities of RA. Thus, synovial fluid and plasma miRNAs have potential as diagnostic biomarkers for RA and OA and as a tool for the analysis of their pathogenesis.
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