title: Altered expression of circulating microRNA in plasma of patients with primary osteoarthritis and in silico analysis of their pathways.
abstract: OBJECTIVE
  To analyze a set of circulating microRNA (miRNA) in plasma from patients with primary Osteoarthritis (OA) and describe the biological significance of altered miRNA in OA based on an in silico analysis of their target genes.
  
  
  METHODS
  miRNA expression was analyzed using TaqMan Low Density Arrays and independent assays. The search for potential messenger RNA (mRNA) targets of the differentially expressed miRNA was performed by means of the miRWalk and miRecords database; we conducted the biological relevance of the predicted miRNA targets by pathway analysis with the Reactome and DAVID databases.
  
  
  RESULTS
  We measured the expression of 380 miRNA in OA; 12 miRNA were overexpressed under the OA condition (p value, ≤0.05; fold change, >2). These results were validated by the detection of some selected miRNA by quantitative PCR (qPCR). In silico analysis showed that target messenger RNA (mRNA) were potentially regulated by these miRNA, including genes such as SMAD1, IL-1B, COL3A, VEGFA, and FGFR1, important in chondrocyte maintenance and differentiation. Some metabolic pathways affected by the miRNA: mRNA ratio are signaling Bone morphogenetic proteins (BMP), Platelet-derived growth factor (PDGF), and Nerve growth factor (NGF), these latter two involved in the process of pain.
  
  
  CONCLUSIONS
  We identified 12 miRNA in the plasma of patients with primary OA. Specific miRNA that are altered in the disease could be released into plasma, either due to cartilage damage or to an inherent cellular mechanism. Several miRNA could regulate genes and pathways related with development of the disease; eight of these circulating miRNA are described, to our knowledge, for first time in OA.
authors.affiliation: Department of Genetics, Instituto Nacional de Rehabilitación (INR), Mexico City, Mexico.
authors.forename: Verónica M
authors.initials: VM
authors.lastname: Borgonio Cuadra
authors.affiliation: Department of Genetics, Instituto Nacional de Rehabilitación (INR), Mexico City, Mexico.
authors.forename: Norma Celia
authors.initials: NC
authors.lastname: González-Huerta
authors.affiliation: Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico.
authors.forename: Sandra
authors.initials: S
authors.lastname: Romero-Córdoba
authors.affiliation: Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Hidalgo-Miranda
authors.affiliation: Department of Genetics, Instituto Nacional de Rehabilitación (INR), Mexico City, Mexico.
authors.forename: Antonio
authors.initials: A
authors.lastname: Miranda-Duarte
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010003:Osteoarthritis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D015398:Signal Transduction
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger