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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11 Scopus citations

Abstract

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
Volume96
Issue number6
DOIs
Publication statusPublished - Jun 2017
Externally publishedYes

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Keywords

  • 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

Cite this

Wisitrasameewong, W., Kajiya, M., Movila, A., Rittling, S., Ishii, T., Suzuki, M., ... 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