Volume 5 Supplement 3

3rd World Congress of the Global Arthritis Research Network (GARN): International Arthritis Summit

Open Access

CD44 regulates bone erosion and osteoclastogenesis in arthritis

  • G Schett1,
  • S Hayer1,
  • K Redlich1,
  • EF Wagner2,
  • G Kollias3,
  • G Steiner1 and
  • JS Smolen1
Arthritis Res Ther20035(Suppl 3):125

https://doi.org/10.1186/ar926

Published: 12 September 2003

Objective

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

Methods

To elucidate the role of CD44 in arthritis, human tumour necrosis factor 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 in hTNFtg controls. In addition, a 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 due to its regulatory role on osteoclasts.

Authors’ Affiliations

(1)
Division of Rheumatology, Department of Internal Medicine III, University of Vienna
(2)
Research Institute for Molecular Pathology
(3)
Institute of Immunology, Alexander Fleming Biomedical Sciences Research Center

Copyright

© The Author(s) 2003

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