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Hypoxia inducible factor (HIF) in rheumatology: low O2! See what HIF can do!
  1. T Gaber1,
  2. R Dziurla1,
  3. R Tripmacher1,
  4. G R Burmester2,
  5. F Buttgereit1
  1. 1Department of Rheumatology and Clinical Immunology, Charité University Hospital, Humboldt University, and Deutsches Rheuma-Forschungszentrum Berlin, Schumannstrasse 20/21, 10117 Berlin, Germany
  2. 2Department of Rheumatology and Clinical Immunology, Charité University Hospital, Humboldt University, Schumannstrasse 20/21, 10117 Berlin, Germany
  1. Correspondence to:
    Professor F Buttgereit
    Department of Rheumatology and Clinical Immunology, Charité University Hospital, Schumannstrasse 20/21, 10117 Berlin, Germany;


Maintenance of oxygen homoeostasis is the basic principle in cell proliferation, differentiation, survival, and function in all higher organisms. The transcription factor, HIF (hypoxia inducible factor) has a central role in oxygen homoeostasis, and is indispensably linked to energy metabolism. Abnormally reduced oxygen concentrations leading to dysfunctional cell metabolism are found in rheumatoid arthritis and hence, knowledge of the molecular adaptive responses to hypoxia and the involvement of HIF in the pathogenesis of RA are interesting.

  • AIA, adjuvant induced arthritis
  • ARNT, aryl hydrocarbon receptor nuclear translocator
  • bHLH, basic helix-loop-helix
  • CIA, collagen induced arthritis
  • COX-2, cyclo-oxygenase-2
  • CTAD, C-terminal transactivation domain
  • CTL, cytotoxic T lymphocyte
  • EC, endothelial cells
  • EPO, erythropoietin
  • FIH, factor inhibiting HIF-1
  • HIF, hypoxia inducible factor
  • HSP, heat shock protein
  • IL, interleukin
  • MAPK, mitogen activated protein kinase
  • MMP, matrix metalloproteinase
  • ODD, oxygen dependent degradation domain
  • PHD, prolyl hydroxylase domain-containing protein
  • PI3K, phosphatidylinositol 3-kinase
  • pVHL, von Hippel-Lindau tumour suppressor protein
  • RA, rheumatoid arthritis
  • ROS/RNS, reactive oxygen and nitrogen species
  • SDF-1, stromal cell derived factor 1
  • TNFα, tumour necrosis factor α
  • VEGF, vascular endothelial growth factor
  • energy metabolism
  • hypoxia
  • hypoxia inducible factor
  • oxygen homoeostasis
  • rheumatoid arthritis

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