Cytoskeletal rearrangements in synovial fibroblasts as a novel pathophysiological determinant of modeled rheumatoid arthritis

Vassilis Aidinis, Piero Carninci, Maria Armaka, Walter Witke, Vaggelis Harokopos, Norman Pavelka, Dirk Koczan, Christos Argyropoulos, Maung Maung Thwin, Steffen Möller, Waki Kazunori, Ponnampalam Gopalakrishnakone, Paola Ricciardi-Castagnoli, Hans Jürgen Thiesen, Yoshihide Hayashizaki, George Kollias

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

Rheumatoid arthritis is a chronic inflammatory disease with a high prevalence and substantial socioeconomic burden. Despite intense research efforts, its aetiology and pathogenesis remain poorly understood. To identify novel genes and/or cellular pathways involved in the pathogenesis of the disease, we utilized a well-recognized tumour necrosis factor-driven animal model of this disease and performed high-throughput expression profiling with subtractive cDNA libraries and oligonucleotide microarray hybridizations, coupled with independent statistical analysis. This twin approach was validated by a number of different methods in other animal models of arthritis as well as in human patient samples, thus creating a unique list of disease modifiers of potential therapeutic value. Importantly, and through the integration of genetic linkage analysis and Gene Ontology-assisted functional discovery, we identified the gelsolin-driven synovial fibroblast cytoskeletal rearrangements as a novel pathophysiological determinant of the disease.

Original languageEnglish
Pages (from-to)455-466
Number of pages12
JournalPLoS Genetics
Volume1
Issue number4
DOIs
Publication statusPublished - 2005

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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