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

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. © international & american associations for dental research.