title: Large-scale gene expression profiling reveals major pathogenetic pathways of cartilage degeneration in osteoarthritis.
abstract: OBJECTIVE
  Despite many research efforts in recent decades, the major pathogenetic mechanisms of osteoarthritis (OA), including gene alterations occurring during OA cartilage degeneration, are poorly understood, and there is no disease-modifying treatment approach. The present study was therefore initiated in order to identify differentially expressed disease-related genes and potential therapeutic targets.
  
  
  METHODS
  This investigation consisted of a large gene expression profiling study performed based on 78 normal and disease samples, using a custom-made complementary DNA array covering >4,000 genes.
  
  
  RESULTS
  Many differentially expressed genes were identified, including the expected up-regulation of anabolic and catabolic matrix genes. In particular, the down-regulation of important oxidative defense genes, i.e., the genes for superoxide dismutases 2 and 3 and glutathione peroxidase 3, was prominent. This indicates that continuous oxidative stress to the cells and the matrix is one major underlying pathogenetic mechanism in OA. Also, genes that are involved in the phenotypic stability of cells, a feature that is greatly reduced in OA cartilage, appeared to be suppressed.
  
  
  CONCLUSIONS
  Our findings provide a reference data set on gene alterations in OA cartilage and, importantly, indicate major mechanisms underlying central cell biologic alterations that occur during the OA disease process. These results identify molecular targets that can be further investigated in the search for therapeutic interventions.
authors.affiliation: Osteoarticular and Arthritis Research, Institute of Pathology, University of Leipzig, Liebigstrasse 26, D-04103 Leipzig, Germany. thomas.aigner@medizin.uni-leipzig.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Aigner
authors.forename: Katrin
authors.initials: K
authors.lastname: Fundel
authors.forename: Joachim
authors.initials: J
authors.lastname: Saas
authors.forename: Pia M
authors.initials: PM
authors.lastname: Gebhard
authors.forename: Jochen
authors.initials: J
authors.lastname: Haag
authors.forename: Tilo
authors.initials: T
authors.lastname: Weiss
authors.forename: Alexander
authors.initials: A
authors.lastname: Zien
authors.forename: Franz
authors.initials: F
authors.lastname: Obermayr
authors.forename: Ralf
authors.initials: R
authors.lastname: Zimmer
authors.forename: Eckart
authors.initials: E
authors.lastname: Bartnik
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002356:Cartilage / Q000473:pathology*; D002454:Cell Differentiation; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D016000:Cluster Analysis; D016172:DNA Fingerprinting; D004734:Energy Metabolism / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods* / Q000592:standards; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D015203:Reproducibility of Results; D012720:Severity of Illness Index
chemical_list: D005819:Genetic Markers