title: Epigenetic differences in human cartilage between mild and severe OA.
abstract: The development of osteoarthritis (OA) depends on genetic and environmental factors, which influence the biology of the chondrocyte via epigenetic regulation. Changes within the epigenome might lead the way to discovery of new pathogenetic pathways. We performed a genome-wide methylation screening to identify potential differences between paired mild and severe osteoarthritic human cartilage. Sixteen female patients suffering from OA underwent total knee joint replacement. Cartilage specimens collected from corresponding macroscopically undamaged and from damaged areas were processed for DNA extraction and histology to evaluate the histological grading of the disease. Paired specimens were analysed for the methylation status of the whole genome using human promoter microarrays (Agilent, Santa Clara, CA). Selected target genes were then validated via methylation-specific qPCR. One thousand two hundred and fourteen genetic targets were identified differentially methylated between mild and severe OA. One thousand and seventy of these targets were found hypermethylated and 144 hypomethylated. The descriptive analysis of these genes by Gene Ontology (GO), KEGG pathway and protein domain analyses points to pathways of development and differentiation. We identified a list of genes which are differently methylated in mild and severe OA cartilage. Within the pathways of growth and development new therapeutic targets might arise by improving our understanding of pathogenetic mechanisms in OA.
authors.affiliation: Department of Rheumatology and Immunology, Medical University Graz, Austria.
authors.forename: Florentine C
authors.initials: FC
authors.lastname: Moazedi-Fuerst
authors.forename: Manuela
authors.initials: M
authors.lastname: Hofner
authors.forename: Gerald
authors.initials: G
authors.lastname: Gruber
authors.forename: Andreas
authors.initials: A
authors.lastname: Weinhaeusel
authors.forename: Martin H
authors.initials: MH
authors.lastname: Stradner
authors.forename: Hannes
authors.initials: H
authors.lastname: Angerer
authors.forename: Daniela
authors.initials: D
authors.lastname: Peischler
authors.forename: Birgit
authors.initials: B
authors.lastname: Lohberger
authors.forename: Mathias
authors.initials: M
authors.lastname: Glehr
authors.forename: Andreas
authors.initials: A
authors.lastname: Leithner
authors.forename: Markus
authors.initials: M
authors.lastname: Sonntagbauer
authors.forename: Winfried B
authors.initials: WB
authors.lastname: Graninger
mesh_terms: D000368:Aged; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics; D002356:Cartilage / Q000378:metabolism*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D016212:Transforming Growth Factor beta / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000502:physiology
chemical_list: D055419:Bone Morphogenetic Protein 7; D016212:Transforming Growth Factor beta
keywords: methylation; osteoarthritis; whole-genome array