Functional Genetic and Genomic Analysis of Modeled Arthritis

  • Eleni Douni
  • Maria Armaka
  • Dimitris L. Kontoyiannis
  • George Kollias
Part of the Advances in Experimental Medicine and Biology book series (volume 602)

Rheumatoid Arthritis (RA) is a chronic inflammatory disease, where pathological interactions between synovial fibroblasts, inflammatory infiltrates and osteoclasts mediate destruction of the inflamed joint. RA and other inflammatory bone diseases illustrate the close link between bone biology and immunology. There is growing evidence that certain molecules regulate both the skeletal and immune systems. Among these factors, tumor necrosis factor (TNF) has received great attention because of its position at the apex of the pro-inflammatory cytokine cascade, which is responsible for the development of inflammatory diseases such as RA and inflammatory bowel disease (IBD). TNF is expressed at high levels in inflamed synovium from RA patients (Saxne, Palladino, Heinegard, et al. 1988; Brennan, Chantry, Jackson, et al. 1989; Firestein, Alvaro-Gracia, and Maki 1990; Feldmann, Brennan, and Maini 1996) where it has pleiotropic functions such as the induction of joint inflammation, the proliferation of synovial fibroblasts (SFs) (Butler, Piccoli, Hart, et al. 1988), the destruction of cartilage by induction of collagenase (Dayer, Beutler, and Cerami 1985) and inhibition of proteoglycan synthesis by articular chondrocytes (Saklatvala 1986). In addition, TNF has a central role in bone pathophysiology by stimulating osteoclastogenesis and bone resorption, while stimultaneously inhibiting the function of bone-forming osteoblasts (Nanes 2003). Experimental studies in animal models of arthritis offer critical information regarding the specific function of TNF and its receptors, TNFRI and TNFRII (Douni, Akassoglou, Alexopoulou, et al. 1995). Particularly, transgenic mice overexpressing human TNF developed an erosive inflammatory arthritis closely resembling human RA (Keffer, Probert, Cazlaris, et al. 1991) and foreshadowed the remarkable effectiveness of anti-TNF therapy in RA (Elliott, Maini, Feldmann, et al. 1993). In this review, we describe the cellular and molecular pathways involved in the pathogenesis of TNF-mediated arthritis in animal models generated by our research group in the past.


Rheumatoid Arthritis Tumor Necrosis Factor Synovial Fibroblast Model Arthritis Mature Osteoclast 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Eleni Douni
    • 1
  • Maria Armaka
    • 1
  • Dimitris L. Kontoyiannis
    • 1
  • George Kollias
    • 1
  1. 1.Institute of ImmunologyBiomedical Sciences Research Center “Alexander Fleming”Greece

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