title: Genome-wide DNA methylation analysis of articular chondrocytes reveals a cluster of osteoarthritic patients.
abstract: OBJECTIVE
  Alterations in DNA methylation patterns have been found to correlate with several diseases including osteoarthritis (OA). The aim of this study was to identify, for the first time, the genome-wide DNA methylation profiles of human articular chondrocytes from OA cartilage and healthy control cartilage samples.
  
  
  METHODS
  DNA methylation profiling was performed using Illumina Infinium HumanMethylation27 in 25 patients with OA and 20 healthy controls. Subsequent validation was performed by genome-wide expression analysis using the Affymetrix Human Gene 1.1 ST array in an independent cohort of 24 patients with OA. Finally, the most consistent genes in both assays were amplified by quantitative reverse transcriptase PCR in a validation cohort of 48 patients using microfluidic real-time quantitative PCR. Appropriate bioinformatics analyses were carried out using R bioconductor software packages and qBase plus software from Biogazelle.
  
  
  RESULTS
  We found 91 differentially methylated (DM) probes, which permitted us to separate patients with OA from healthy controls. Among the patients with OA, we detected 1357 DM probes that identified a tight cluster of seven patients who were different from the rest. This cluster was also identified by genome-wide expression in which 450 genes were differentially expressed. Further validation of the most consistent genes in an independent cohort of patients with OA permitted us to identify this cluster, which was characterised by increased inflammatory processes.
  
  
  CONCLUSIONS
  We were able to identify a tight subgroup of patients with OA, characterised by an increased inflammatory response that could be regulated by epigenetics. The identification and isolation of this subgroup may be critical for the development of effective treatment and disease prevention.
authors.affiliation: Rheumatology Division, INIBIC-Complejo Hospitalario Universitario A Coruña (CHUAC), , Coruña, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Fernández-Tajes
authors.forename: Angel
authors.initials: A
authors.lastname: Soto-Hermida
authors.forename: Maria E
authors.initials: ME
authors.lastname: Vázquez-Mosquera
authors.forename: Estefania
authors.initials: E
authors.lastname: Cortés-Pereira
authors.forename: Alejandro
authors.initials: A
authors.lastname: Mosquera
authors.forename: Mercedes
authors.initials: M
authors.lastname: Fernández-Moreno
authors.forename: Natividad
authors.initials: N
authors.lastname: Oreiro
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-López
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Fernández
authors.forename: Ignacio
authors.initials: I
authors.lastname: Rego-Pérez
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Blanco
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002358:Cartilage, Articular / Q000378:metabolism*; D016022:Case-Control Studies; D019902:Chondrocytes / Q000378:metabolism*; D016000:Cluster Analysis; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
keywords: Chondrocytes; Knee Osteoarthritis; Osteoarthritis