Cytoskeletal rearrangements in synovial fibroblasts as a novel pathophysiological determinant of modeled rheumatoid arthritis.
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.
Aidinis
Vassilis
V
Institute of Immunology, Alexander Fleming Biomedical Sciences Research Center, Athens, Greece. V.Aidinis@Fleming.gr
Carninci
Piero
P
Armaka
Maria
M
Witke
Walter
W
Harokopos
Vaggelis
V
Pavelka
Norman
N
Koczan
Dirk
D
Argyropoulos
Christos
C
Thwin
Maung-Maung
MM
Möller
Steffen
S
Waki
Kazunori
K
Kazunori
Waki
W
Gopalakrishnakone
Ponnampalam
P
Ricciardi-Castagnoli
Paola
P
Thiesen
Hans-Jürgen
HJ
Hayashizaki
Yoshihide
Y
Kollias
George
G
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
D014409:Tumor Necrosis Factor-alpha