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CD44 regulates bone erosion and osteoclastogenesis in arthritis
Arthritis Res Thervolume 5, Article number: 125 (2003)
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.
To elucidate the role of CD44 in arthritis, human tumour necrosis factor transgenic (hTNFtg) mice were crossed with CD44 knockout mice.
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.
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.