MicroRNAs (miRNAs) are a group of endogenous non-coding RNAs that regulate gene expression. Alteration in miRNA expression results in changes in the profile of genes involving a range of biological processes, contributing to numerous human disorders. With high stability in human fluids, miRNAs in the circulation are considered as promising biomarkers for diagnosis, as well as prognosis of disease. In addition, the translation of miRNA-based therapy from a research setting to clinical application has huge potential. The aim of the current review is to: (i) discuss how miRNAs traffic intracellularly and extracellularly; (ii) emphasize the role of circulating miRNAs as attractive potential biomarkers for diagnosis and prognosis; (iii) describe how circulating microRNA can be measured, emphasizing technical problems that may influence their relative levels; (iv) highlight some of the circulating miRNA panels available for clinical use; (v) discuss how miRNAs could be utilized as novel therapeutics, and finally (v) update those miRNA-based therapeutics clinical trials that could potentially lead to a breakthrough in the treatment of different human pathologies.

versus OOA; SNORD74 and SNORD77. The latter was accompanied by an increase in GAS5 expression in OA. P53 signalling has been implicated in cartilage ageing and OA. The expression of SNHG1, which along with its intronic snoRNAs have previously been identified as being repressed by p53 activation was reduced in ageing and increased in OA in parallel with one of its intronic snoRNAs SNORD26. HAGR identified eight agerelated host genes, including RLP13A, RPS12 in Y versus ON contrast. Six host genes were identified as age-related in the ON1 versus ON2 contrast, including RPL13A and RPS12. The top canonical pathways identified from Y versus ON host genes were EIF2 (p¼1.7E-25), mTOR signalling (p¼2.1E-09) and regulation of EIF4 and p70S6K signalling (p¼7.1E-09) and for ON versus OOA were EIF2 signalling (p¼3.1E-12), regulation of EIF4 and p70S6K signalling (p¼3.6E-04) and mTOR signalling (p¼7.2E-04). The top networks identified in Y versus ON was 'cell death and survival and organismal injury', and for ON versus OOA was 'immunological disease'. Conclusions: Previously it was thought that as many host genes contained short, poorly conserved, open reading frames that they had no function other than carry the snoRNAs sequence within their introns. However work in cancer has identified that some host genes have roles in tumorigenesis and cell fate. Many of the protein coding snoRNA host genes are involved in protein synthesis enabling co-regulation of snoRNAs and proteins implicated in translation. mTOR signalling, is implicated in cartilage homeostasis and cartilage degeneration associated with OA. This was one of the principal pathways that host genes contributed to and host genes were within multiple levels of the signalling pathway. Our work points to additional, as yet undefined roles for some of these snoRNA host genes in cartilage ageing and OA, both through the production of the snoRNAs which they express, and through functions of the genes themselves. THEPurpose: Synovitis is a characteristic feature of both early and endstage OA. However, the cellular mechanisms that regulate synovial tissue inflammation are poorly understood. Importantly, we recently identified through Next Generation Sequencing (NGS) several long non coding RNAs (lncRNAs) that were associated with the IL-1b inflammatory response in OA chondrocytes, and which regulated the secretion of pro-inflammatory cytokines including IL-6. The purpose of the present study was firstly to identify lncRNAs expressed in fibroblast-like synoviocytes (FLS) that were associated with inflammatory OA synovial tissue. Secondly to examine their expression in OA synovium compared to non-OA synovial tissue, and thirdly to determine whether modulation of the expression of an inflammatory-associated lncRNA affected the phenotype of isolated OA FLS cells. Methods: Synovial tissue was collected from end-stage hip OA patients and from neck of femur fracture patients without OA (NOF#) undergoing total hip arthroplasty (NRES 14/ES/1044). Fibroblast-like synoviocytes (FLS) were...

MiR-3085-3p was shown to play a crucial role in cartilage biology, with potential impacts in osteoarthritis (OA). Insight into this miRNA function could be of practical importance for future miRNA-based therapy, however, little is known regarding the biological roles of this miRNA. The physiologic function of an individual miRNA is dictated through its mRNA targets, and as SCIN (scinderin, also known as adseverin) was reported to be involved in chondrocyte differentiation, maturation, and phenotype maintenance, this study aimed to prove SCIN is a direct target of miRNA- 3085-3p. Bioinformatics algorithms were utilized for predicting their interacting sites. Gain- and loss of- function experiments with miRNA-3085-3p were performed and SCIN expression was measured by real-time RT-PCR. SCIN 3'UTR regions harboring either the miR-3085-3p seed site or its mutant version were cloned into pmirGLO downstream of a reporter firefly luciferase encoding gene. The effect of miR-3085-3p on this region was determined by the luciferase assay. Four binding sites of miR-3085- 3p in SCIN 3'UTR were identified. SCIN expression level was found to be inversely correlated with the level of miRNA-3085-3p. MiR3085-3p directly binds to its binding sites in SCIN 3' UTR. These data suggest that SCIN is the direct target of miR-3085-3p in chondrocyte cells.