Volume 6 Supplement 1

24th European Workshop for Rheumatology Research

Open Access

CD44 regulates bone erosion and osteoclastogenesis in arthritis

  • S Hayer1,
  • B Goertz1,
  • J Zwerina1,
  • K Redlich1,
  • O Hoffmann2,
  • M Amling3,
  • F Hilberg4,
  • G Kollias5,
  • G Steiner1,
  • EF Wagner6,
  • JS Smolen1 and
  • G Schett1
Arthritis Res Ther20046(Suppl 1):52

DOI: 10.1186/ar1094

Received: 16 January 2004

Published: 24 February 2004

Background and Objective

CD44 mediates cell-matrix interaction and is thought to play a role in cell adhesion, fusion and migration. Blocking of CD44 is considered as potential target in the therapy of rheumatoid arthritis.

Methods

To elucidate the role of CD44 in arthritis, human TNF transgenic (hTNFtg) mice were crossed with CD44 knockout mice.

Results

Clinical evaluation revealed a significantly increased severity of arthritis in CD44-/- hTNFtg mice than in hTNFtg mice. Wild-type mice and CD44-/- mice were normal. Histologically, bone destruction was dramatically increased in the arthritic paws of CD44-/- hTNFtg mice. Changes were based on a significant increase of size and number of osteoclasts in the synovial inflammatory tissue. Ex vivo analysis of osteoclastogenesis revealed that osteoclasts differentiated more rapidly and were increased in size and number in CD44-/- hTNFtg mice compared with hTNFtg controls. In addition, bone resorption assay showed increased 'pit' formation by osteoclasts of CD44-/- hTNFtg mice.

Conclusion

CD44 deficiency does not block but rather increases the severity of TNF-mediated arthritis. This was due to increased bone damage caused by deregulation of osteoclastogenesis. We conclude that CD44 is of benefit for TNF-mediated arthritis because of its regulatory role on osteoclasts.

Authors’ Affiliations

(1)
Division of Rheumatology, Department of Internal Medicine III, University of Vienna
(2)
Institute of Pharmacology and Toxicology, University of Vienna
(3)
Department of Experimental Trauma Surgery, Hamburg University School of Medicine
(4)
Boehringer Ingelheim
(5)
Molecular Genetics Laboratory, Institute of Immunology, Alexander Fleming Biomedical Sciences Research Center
(6)
Research Institute of Molecular Pathology, University of Vienna

Copyright

© BioMed Central Ltd 2004

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