title: Functional genomics of fibroblasts.
abstract: OBJECTIVE
  Successful analysis of the pathophysiology of rheumatoid arthritis requires the functional understanding of interactions between different cell types and the cell matrix, intracellular signaling pathways, as well as between cartilage, bone, and synovium in rheumatoid arthritis. During the review period, molecular biology has provided and used a growing number of tools to screen the genome such as gene and protein chips, haplotype analysis, and single nucleotide polymorphism analysis, resulting in various novel findings with considerable impact on the overall understanding of rheumatoid arthritis.
  
  
  RESULTS
  Key issues that have been addressed and elucidated by numerous research groups are the regulation and modulation of synovial fibroblast metabolism and activation by proinflammatory cytokines and chemokines. In addition, examination of adhesion processes and neoangiogenesis has revealed new insights into the interaction network between rheumatoid synovial fibroblasts and the surrounding matrix and cells. Finally, a more detailed view of activation of these fibroblasts has been obtained by analysis of the molecular balance between cellular activation and regulation of apoptosis.
  
  
  CONCLUSIONS
  Although high throughput molecular analysis methods provided an ample amount of novel data, it needs to be stressed that a one-method approach of gene expression (eg, by array analysis) is not sufficient to validate the gene/gene product as a new therapeutic target. Therefore, the next steps are the so-called functional genomics or functionomics, which intend to reveal relations between the obtained data and to unveil their interactions for a better understanding of the pathogenesis and the mechanisms that are operative in rheumatoid arthritis.
authors.affiliation: Department of Internal Medicine I, University of Regensburg, D-93042 Regensburg, Germany. ulf.mueller-ladner@klinik.uni-regensburg.de
authors.forename: Elena
authors.initials: E
authors.lastname: Neumann
authors.forename: Renate E
authors.initials: RE
authors.lastname: Gay
authors.forename: Steffen
authors.initials: S
authors.lastname: Gay
authors.forename: Ulf
authors.initials: U
authors.lastname: Müller-Ladner
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002455:Cell Division / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology* / Q000502:physiology; D023281:Genomics / Q000379:methods*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D020782:Matrix Metalloproteinases / Q000276:immunology*; D009389:Neovascularization, Pathologic / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D015815:Cell Adhesion Molecules; D020782:Matrix Metalloproteinases