title: Cytoskeletal rearrangements in synovial fibroblasts as a novel pathophysiological determinant of modeled rheumatoid arthritis.
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.
authors.affiliation: Institute of Immunology, Alexander Fleming Biomedical Sciences Research Center, Athens, Greece. V.Aidinis@Fleming.gr
authors.forename: Vassilis
authors.initials: V
authors.lastname: Aidinis
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
authors.forename: Maria
authors.initials: M
authors.lastname: Armaka
authors.forename: Walter
authors.initials: W
authors.lastname: Witke
authors.forename: Vaggelis
authors.initials: V
authors.lastname: Harokopos
authors.forename: Norman
authors.initials: N
authors.lastname: Pavelka
authors.forename: Dirk
authors.initials: D
authors.lastname: Koczan
authors.forename: Christos
authors.initials: C
authors.lastname: Argyropoulos
authors.forename: Maung-Maung
authors.initials: MM
authors.lastname: Thwin
authors.forename: Steffen
authors.initials: S
authors.lastname: Möller
authors.forename: Kazunori
authors.initials: K
authors.lastname: Waki
authors.forename: Waki
authors.initials: W
authors.lastname: Kazunori
authors.forename: Ponnampalam
authors.initials: P
authors.lastname: Gopalakrishnakone
authors.forename: Paola
authors.initials: P
authors.lastname: Ricciardi-Castagnoli
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Thiesen
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: George
authors.initials: G
authors.lastname: Kollias
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000503:physiopathology; D003599:Cytoskeleton / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D015723:Gene Library; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D040641:Quantitative Trait Loci; D013583:Synovial Membrane / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha