RESUMEN
OBJECTIVES: 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.
RESUMEN
As epigenetic regulators of gene expression, circulating micro-RiboNucleic Acids (miRNAs) have been described in several bone diseases as potential prognostic markers. The aim of our study was to identify circulating miRNAs potentially associated with the severity of osteogenesis imperfecta (OI) in three steps. We have screened by RNA sequencing for the miRNAs that were differentially expressed in sera of a small group of OI patients versus controls and then conducted a validation phase by RT-qPCR analysis of sera of a larger patient population. In the first phase of miROI, we found 79 miRNAs that were significantly differentially expressed. We therefore selected 19 of them as the most relevant. In the second phase, we were able to validate the significant overexpression of 8 miRNAs in the larger OI group. Finally, we looked for a relationship between the level of variation of the validated miRNAs and the clinical characteristics of OI. We found a significant difference in the expression of two microRNAs in those patients with dentinogenesis imperfecta. After reviewing the literature, we found 6 of the 8 miRNAs already known to have a direct action on bone homeostasis. Furthermore, the use of a miRNA-gene interaction prediction model revealed a 100% probability of interaction between 2 of the 8 confirmed miRNAs and COL1A1 and/or COL1A2. This is the first study to establish the miRNA signature in OI, showing a significant modification of miRNA expression potentially involved in the regulation of genes involved in the physiopathology of OI. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).