The dendritic cell-specific transmembrane protein DC-STAMP is essential for osteoclast fusion and osteoclast bone-resorbing activity
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-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.
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Under the influence of the RANKL/RANK interaction, NFATc1 induces the expression of DC-STAMP, which is crucial for the fusion of osteoclast precursors.
“Under the influence of the RANKL/RANK interaction, NFATc1 also induces the expression of DC-STAMP, which is crucial for the fusion of osteoclast precursors [91, 92].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [91]
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- Authors
- Miyamoto, T.
- Affiliations
- Keio University (JP)
- Corresponding author
- Miyamoto, Takeshi
- ORCID
- Miyamoto, Takeshi
- Venue
- Modern Rheumatology
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-12
- Volume
- 16
- Issue
- 6
- Pages
- 341-342
- ISSN
- 1439-7595 (ISSN-L)
- 1439-7609
- OpenAlex
- W1977949170
- Cited by
- 62
- References
- 10
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 8 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 5 · 2014: 1 · 2013: 1 · 2012: 5
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Modern Rheumatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
- Keywords
- DC-STAMP, osteoclasts, osteoclast fusion, multinucleation, bone resorption, osteopetrosis, rheumatoid arthritis, seven-transmembrane proteins, osteoclastogenesis
- MeSH terms
- Animals, Arthritis, Rheumatoid, Bone Resorption, Cell Fusion, Dendritic Cells, Membrane Proteins, Nerve Tissue Proteins, Osteoclasts, Osteopetrosis, Giant Cells, Mice, Knockout, Mice
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