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

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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.

• Document type: Journal article
• Source: JOURNAL OF DENTAL RESEARCH; v. 96, n. 6, p. 685-693, JUN 2017.
• Web of Science Citations: 10

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-, interleukin-1, 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. (AU)

• FAPESP's process: 15/07107-0 - The possible anti-bone formation role of semaforina 4D expressed in the context of periapical periodontitis
• Grantee: Mariane Maffei Azuma
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate