title: Characterization of microRNA expression profiles in normal and osteoarthritic human chondrocytes.
abstract: BACKGROUND
  Osteoarthritis (OA) is a multifactorial disease characterized by destruction of the articular cartilage due to environmental, mechanical and genetic components. The genetics of OA is complex and is not completely understood. Recent works have demonstrated the importance of microRNAs (miRNAs) in cartilage function. MiRNAs are a class of small noncoding RNAs that regulate gene expression and are involved in different cellular process: apoptosis, proliferation, development, glucose and lipid metabolism. The aim of this study was to identify and characterize the expression profile of miRNAs in normal and OA chondrocytes and to determine their role in the OA.
  
  
  METHODS
  Chondrocytes were moved to aggregate culture and evaluated using histological and qPCR techniques. miRNAs were isolated and analyzed using the Agilent Human miRNA Microarray.
  
  
  RESULTS
  Of the 723 miRNAs analyzed, 7 miRNAs showed a statistically significant differential expression. Amongst these 7 human miRNAs, 1 was up-regulated in OA chondrocytes (hsa-miR-483-5p) and 6 were up-regulated in normal chondrocytes (hsa-miR-149*, hsa-miR-582-3p, hsa-miR-1227, hsa-miR-634, hsa-miR-576-5p and hsa-miR-641). These profiling results were validated by the detection of some selected miRNAs by qPCR. In silico analyses predicted that key molecular pathways potentially altered by the miRNAs differentially expressed in normal and OA chondrocytes include TGF-beta, Wnt, Erb and mTOR signalling; all of them implicated in the development, maintenance and destruction of articular cartilage.
  
  
  CONCLUSIONS
  We have identified 7 miRNAs differentially expressed in OA and normal chondrocytes. Our potential miRNA target predictions and the signalling cascades altered by the differentially expressed miRNAs supports the potential involvement of the detected miRNAs in OA pathology. Due to the importance of miRNA in mediating the translation of target mRNA into protein, the identification of these miRNAs differentially expressed in normal and OA chondrocyte micropellets could have important diagnostic and therapeutic potential. Further studies are needed to know the function of these miRNAs, including the search of their target mRNA genes, which could lead to the development of novel therapeutic strategies for the OA treatment.
authors.affiliation: Department of Medicine, INIBIC-University of A Coruña, A Coruña, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Díaz-Prado
authors.forename: Claudia
authors.initials: C
authors.lastname: Cicione
authors.forename: Emma
authors.initials: E
authors.lastname: Muiños-López
authors.forename: Tamara
authors.initials: T
authors.lastname: Hermida-Gómez
authors.forename: Natividad
authors.initials: N
authors.lastname: Oreiro
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-López
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Blanco
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D019295:Computational Biology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000235:genetics* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results
chemical_list: D035683:MicroRNAs