DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption

W Wisitrasameewong, M Kajiya, A Movila, S Rittling, T Ishii, M Suzuki, S Matsuda, Y Mazda, M R Torruella, M M Azuma, K Egashira, M O Freire, H Sasaki, C Y Wang, X Han, M A Taubman, T Kawai

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14 Scopus citations


Dendritic cell-specific transmembrane protein (DC-STAMP) plays a key role in the induction of osteoclast (OC) cell fusion, as well as DC-mediated immune regulation. While DC-STAMP gene expression is upregulated in the gingival tissue with periodontitis, its pathophysiological roles in periodontitis remain unclear. To evaluate the effects of DC-STAMP in periodontitis, anti-DC-STAMP-monoclonal antibody (mAb) was tested in a mouse model of ligature-induced periodontitis ( n = 6-7/group) where Pasteurella pneumotropica ( Pp)-reactive immune response activated T cells to produce receptor activator of nuclear factor kappa-B ligand (RANKL), which, in turn, promotes the periodontal bone loss via upregulation of osteoclastogenesis. DC-STAMP was expressed on the cell surface of mature multinuclear OCs, as well as immature mononuclear OCs, in primary cultures of RANKL-stimulated bone marrow cells. Anti-DC-STAMP-mAb suppressed the emergence of large, but not small, multinuclear OCs, suggesting that DC-STAMP is engaged in the late stage of cell fusion. Anti-DC-STAMP-mAb also inhibited pit formation caused by RANKL-stimulated bone marrow cells. Attachment of ligature to a second maxillary molar induced DC-STAMP messenger RNA and protein, along with elevated tartrate-resistant acid phosphatase-positive (TRAP+) OCs and alveolar bone loss. As we expected, systemic administration of anti-DC-STAMP-mAb downregulated the ligature-induced alveolar bone loss. Importantly, local injection of anti-DC-STAMP-mAb also suppressed alveolar bone loss and reduced the total number of multinucleated TRAP+ cells in mice that received ligature attachment. Attachment of ligature induced significantly elevated tumor necrosis factor-α, interleukin-1β, and RANKL in the gingival tissue compared with the control site without ligature ( P < 0.05), which was unaffected by local injection with either anti-DC-STAMP-mAb or control-mAb. Neither in vivo anti- Pp IgG antibody nor in vitro anti- Pp T-cell response and resultant production of RANKL was affected by anti-DC-STAMP-mAb. This study illustrated the roles of DC-STAMP in promoting local OC cell fusion without affecting adaptive immune responses to oral bacteria. Therefore, it is plausible that a novel therapeutic regimen targeting DC-STAMP could suppress periodontal bone loss.

Original languageEnglish (US)
Pages (from-to)685-693
Number of pages9
JournalJournal of Dental Research
Issue number6
StatePublished - Jun 2017
Externally publishedYes


  • Animals
  • Antibodies, Monoclonal/pharmacology
  • Blotting, Western
  • Bone Resorption/pathology
  • Cell Differentiation
  • Cell Fusion
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation
  • Male
  • Membrane Proteins/antagonists & inhibitors
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins/antagonists & inhibitors
  • Osteoclasts/drug effects
  • Periodontitis/pathology
  • RANK Ligand/pharmacology
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction

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  • Cite this

    Wisitrasameewong, W., Kajiya, M., Movila, A., Rittling, S., Ishii, T., Suzuki, M., Matsuda, S., Mazda, Y., Torruella, M. R., Azuma, M. M., Egashira, K., Freire, M. O., Sasaki, H., Wang, C. Y., Han, X., Taubman, M. A., & Kawai, T. (2017). DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption. Journal of Dental Research, 96(6), 685-693. https://doi.org/10.1177/0022034517690490