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.

In hematopoietic stem cell transplantation (HSCT), when no HLA full-matched donor is available, alternative donors could include one HLA-mismatched donor. Recently, the low expressed HLA-C alleles have been identified as permissive mismatches for the best donor choice. Concerning HLA-A, the degree of variability of expression is poorly understood. Here, we evaluated HLA-A expression in healthy individuals carrying HLA-A*02 allele in different genotypes using flow cytometry and allele-specific quantitative RT-PCR. While an interindividual variability of HLA-A*02 cell surface expression, not due to the allele associated, was observed, no difference of the mRNA expression level was shown, suggesting the involvement of the posttranscriptional regulation. The results of qRT-PCR analyses exhibit a differential expression of HLA-A alleles with HLA-A*02 as the strongest expressed allele independently of the second allele. The associated non-HLA-A*02 alleles were differentially expressed, particularly the HLA-A*31 and HLA-A*33 alleles (strong expression) and the HLA-A*29 (low expression). The presence of specific polymorphisms in the 5 and 3 untranslated regions of the HLA-A*31 and HLA-A*33 alleles could contribute to this high level of expression. As previously described for HLA-C, low-expressed HLA-A alleles, such as HLA-A*29, could be considered as a permissive mismatch, although this needs to be confirmed by clinical studies.Keywords: Allele · Expression · HLA · Hematopoietic stem cell transplantation · Polymorphism Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionHematopoietic stem cell transplantation (HSCT) is now widely used for the treatment of high-risk hematological malignancies, such as acute leukemia. To find a suitable donor, human leukocyte antigen (HLA) typing is performed. In most transplant Correspondence: Dr. Céline René e-mail: celine.rene@inserm.fr centers, a perfect match (10/10) of the ten alleles of the HLA-A, -B, -C, -DQB1, and -DRB1 loci is considered to be the optimal condition for HSCT with unrelated living donors. However, this requirement is fulfilled in just about half of the HSCTs, despite the expansion of international donor registries [1]. For patients lacking HLA-matched unrelated donors, single HLA * These authors contributed equally to this work.www.eji-journal.eu Eur. J. Immunol. 2015. 45: 3454-3463 Molecular immunology 3455 mismatch unrelated donors might be considered as alternative donors. However, the risk of graft versus host disease (GVHD) is increased and overall survival is reduced in patients who receive a graft from a donor with a single mismatch in the HLA class I locus compared with the HLA-matched situation [2,3]. Moreover, the adverse effects on the patient's outcome depend also on the locus carrying the mismatch between donor and recipient [4,5]. In this context, in order to increase the safety of HSCT with HLA-mismatched unrelated donors, a better understanding of the factors that trigger t...

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