IRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, France.
Immunology Department, CHU Montpellier, Montpellier, France.
Front Immunol. 2019 Mar 7;10:375. doi: 10.3389/fimmu.2019.00375. eCollection 2019.
MicroRNAs (miRNAs) are small non-coding single-stranded RNAs that represent important posttranscriptional regulators of protein-encoding genes. In particular, miRNAs play key roles in regulating cellular processes such as proliferation, migration, and cell differentiation. Recently, miRNAs emerged as critical regulators of osteoclasts (OCs) biology and have been involved in OCs pathogenic role in several disorders. OCs are multinucleated cells generated from myeloid precursors in the bone marrow, specialized in bone resorption. While there is a growing number of information on the cytokines and signaling pathways that are critical to control the differentiation of osteoclast precursors (OCPs) into mature OCs, the connection between OC differentiation steps and miRNAs is less well-understood. The present review will first summarize our current understanding of the miRNA-regulated pathways in the sequential steps required for OC formation, from the motility and migration of OCPs to the cell-cell fusion and the final formation of the actin ring and ruffled border in the functionally resorbing multinucleated OCs. Then, considering the difficulty of working on primary OCs and on the generation of robust data we will give an update on the most recent advances in the detection technologies for miRNAs quantification and how these are of particular interest for the understanding of OC biology and their use as potential biomarkers.
微小 RNA(miRNA)是小的非编码单链 RNA,是蛋白质编码基因的重要转录后调控因子。特别是,miRNA 在调节细胞增殖、迁移和细胞分化等细胞过程中发挥关键作用。最近,miRNA 成为破骨细胞(OC)生物学的关键调节因子,并参与了几种疾病中 OC 的致病作用。OC 是骨髓中髓系前体产生的多核细胞,专门负责骨吸收。虽然关于控制破骨细胞前体(OCP)分化为成熟 OC 的细胞因子和信号通路的信息越来越多,但 OC 分化步骤与 miRNA 之间的联系还不太清楚。本综述将首先总结我们目前对 OC 形成所需的连续步骤中 miRNA 调节途径的理解,从 OCP 的运动和迁移到细胞融合以及功能吸收多核 OC 中最终形成的肌动环和皱襞边缘。然后,考虑到对原代 OC 进行研究和生成稳健数据的困难,我们将介绍 miRNA 定量检测技术的最新进展,并介绍这些技术对于理解 OC 生物学及其作为潜在生物标志物的应用的特别关注。