MINIREVIEW
The dendritic cell-specific transmembrane protein DC-STAMP is essential for osteoclast fusion and osteoclast bone-resorbing activity
Authors
Takeshi Miyamoto1
| (1) |
Departments of Cell Differentiation, Orthopedics, and Musculoskeletal Reconstruction and Regeneration Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan |
Received:
June 8, 2006
Accepted:
July 10, 2006
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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 |
