Abstract：
OBJECTIVE: To identify circulating micro-RNAs differentially expressed in patients with erosive hand osteoarthritis (HOA) compared to patients with non-erosive HOA and patients without HOA.
METHODS: In the screening phase, 768 well-characterized micro-RNAs using Taqman low-density array cards were measured in 30 sera from 10 patients with erosive HOA, 10 patients with non-erosive HOA, and 10 controls without HOA, matched for age and body mass index (BMI). In a second step, we validated the micro-RNAs identified at the screening phase (adjusted p value < 0.05 after false discovery rate correction using Benjamini-Hochberg method and literature review) in larger samples (60 patients with erosive HOA and 60 patients without HOA matched for age and BMI).
RESULTS: In the screening phase, we identified 21 down-regulated and 4 up-regulated micro-RNAs of interest between erosive HOA and control groups. Among these, 9 micro-RNAs (miR-373-3p, miR-558, miR-607, miR-653-5p, miR-137 and miR448 were down-regulated, and miR-142-3p, miR-144-3p and miR-34a-5p were up-regulated) were previously described in chondrocytes homeostasis or OA. We found only one significantly down-regulated micro-RNA between erosive and non-erosive HOA. In the validation phase, we showed replication of a single micro-RNA the significant downregulation of miR-196-5p, that had been previously identified in the screening phase among patients with erosive HOA compared to those without HOA. After reviewing the literature and the miRNA-gene interaction prediction model, we found that this microRNA could interact with bone homeostasis and HOXC8, which could explain its role in osteoarthritis.
CONCLUSIONS: We found that miR-196-5p was down-regulated in patients with erosive HOA and some of its targets could explain a role in OA.
METHODS: In the screening phase, 768 well-characterized micro-RNAs using Taqman low-density array cards were measured in 30 sera from 10 patients with erosive HOA, 10 patients with non-erosive HOA, and 10 controls without HOA, matched for age and body mass index (BMI). In a second step, we validated the micro-RNAs identified at the screening phase (adjusted p value < 0.05 after false discovery rate correction using Benjamini-Hochberg method and literature review) in larger samples (60 patients with erosive HOA and 60 patients without HOA matched for age and BMI).
RESULTS: In the screening phase, we identified 21 down-regulated and 4 up-regulated micro-RNAs of interest between erosive HOA and control groups. Among these, 9 micro-RNAs (miR-373-3p, miR-558, miR-607, miR-653-5p, miR-137 and miR448 were down-regulated, and miR-142-3p, miR-144-3p and miR-34a-5p were up-regulated) were previously described in chondrocytes homeostasis or OA. We found only one significantly down-regulated micro-RNA between erosive and non-erosive HOA. In the validation phase, we showed replication of a single micro-RNA the significant downregulation of miR-196-5p, that had been previously identified in the screening phase among patients with erosive HOA compared to those without HOA. After reviewing the literature and the miRNA-gene interaction prediction model, we found that this microRNA could interact with bone homeostasis and HOXC8, which could explain its role in osteoarthritis.
CONCLUSIONS: We found that miR-196-5p was down-regulated in patients with erosive HOA and some of its targets could explain a role in OA.
摘要：
目的：鉴定糜烂性手骨关节炎（HOA）患者与非糜烂性HOA患者和无HOA患者的循环差异表达的微小RNA。
方法：在筛选阶段，使用Taqman低密度阵列卡在10例糜烂性HOA患者的30份血清中测量了768个特征明确的micro-RNAs，10例非糜烂性HOA患者和10例无HOA的对照，年龄和BMI相匹配。第二步,我们在更大样本(60例糜烂性HOA患者和60例无HOA患者,年龄和BMI相匹配)中验证了在筛选阶段鉴定的micro-RNA(使用Benjamini-Hochberg方法和文献综述进行错误发现率校正后校正后p值<0.05).
结果：在筛查阶段，我们在侵蚀性HOA和对照组之间鉴定了21个下调和4个上调的目的微RNA。其中,9个微小RNA（miR-373-3p，miR-558,miR-607,miR-653-5p,miR-137和miR448下调，miR-142-3p，miR-144-3p和miR-34a-5p上调）先前在软骨细胞稳态或OA中描述过。我们发现在侵蚀性和非侵蚀性HOA之间只有一种显著下调的微RNA。在验证阶段，我们显示单个micro-RNA的复制显著下调miR-196-5p，与没有HOA的患者相比，在有糜烂性HOA的患者中，先前已在筛查阶段发现了这一点。在查阅文献和miRNA-基因相互作用预测模型后,我们发现这种microRNA可以与骨稳态和HOXC8相互作用，这可以解释其在骨关节炎中的作用。
结论：我们发现miR-196-5p在糜烂性HOA患者中下调，其一些靶标可以解释在OA中的作用。
方法：在筛选阶段，使用Taqman低密度阵列卡在10例糜烂性HOA患者的30份血清中测量了768个特征明确的micro-RNAs，10例非糜烂性HOA患者和10例无HOA的对照，年龄和BMI相匹配。第二步,我们在更大样本(60例糜烂性HOA患者和60例无HOA患者,年龄和BMI相匹配)中验证了在筛选阶段鉴定的micro-RNA(使用Benjamini-Hochberg方法和文献综述进行错误发现率校正后校正后p值<0.05).
结果：在筛查阶段，我们在侵蚀性HOA和对照组之间鉴定了21个下调和4个上调的目的微RNA。其中,9个微小RNA（miR-373-3p，miR-558,miR-607,miR-653-5p,miR-137和miR448下调，miR-142-3p，miR-144-3p和miR-34a-5p上调）先前在软骨细胞稳态或OA中描述过。我们发现在侵蚀性和非侵蚀性HOA之间只有一种显著下调的微RNA。在验证阶段，我们显示单个micro-RNA的复制显著下调miR-196-5p，与没有HOA的患者相比，在有糜烂性HOA的患者中，先前已在筛查阶段发现了这一点。在查阅文献和miRNA-基因相互作用预测模型后,我们发现这种microRNA可以与骨稳态和HOXC8相互作用，这可以解释其在骨关节炎中的作用。
结论：我们发现miR-196-5p在糜烂性HOA患者中下调，其一些靶标可以解释在OA中的作用。
