MINIREVIEW
The dendritic cell-specific transmembrane protein DC-STAMP is essential for osteoclast fusion and osteoclast bone-resorbing activity

Authors
Takeshi Miyamoto¹

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Received: June 8, 2006 Accepted: July 10, 2006

Abstract
Osteoclasts are bone-resorbing cells that play a critical role for bone destruction in rheumatoid arthritis. It is well known that osteoclasts form multinuclear cells by cell-cell fusion of mononuclear osteoclasts; however, what molecules are required for osteoclast cell-cell fusion, and the role of multinucleation remain uncharacterized. We identified the dendritic cell-specific transmembrane protein DC-STAMP, a putative seven transmembrane protein, and generated DC-STAMP-deficient mice. The cell fusion of
osteoclasts was completely abrogated in DC-STAMPdeficient mice, while the transcription factors required for osteoclast differentiation or osteoclast maturation markers were induced as wild type osteoclasts. Interestingly, boneresorbing activity was reduced in DC-STAMP-deficient osteoclasts compared with wild-type osteoclasts, and DCSTAMP- deficient mice showed osteopetrosis. Thus,
we identified DC-STAMP as an essential molecule for osteoclast cell-cell fusion, and found that multinuclear osteoclasts have a higher bone-resorbing activity than mononuclear osteoclastic cells seen in DC-STAMP-deficient mice.

Key words
Cell fusion, DC-STAMP, Osteoclast, Rheumatoid arthritis