The dendritic cell-specific transmembrane protein DC-STAMP is essential for osteoclast fusion and osteoclast bone-resorbing activity.
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-STAMP-deficient mice, while the transcription factors required for osteoclast differentiation or osteoclast maturation markers were induced as wild type osteoclasts. Interestingly, bone-resorbing activity was reduced in DC-STAMP-deficient osteoclasts compared with wild-type osteoclasts, and DC-STAMP-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.
Miyamoto
Takeshi
T
Department of Cell Differentiation, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. miyamoto@sc.itc.keio.ac.jp
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology; D001862:Bone Resorption / Q000378:metabolism* / Q000473:pathology; D002459:Cell Fusion; D003713:Dendritic Cells / Q000378:metabolism*; D015726:Giant Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D010022:Osteopetrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology
C499636:DC-STAMP protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins