OC-STAMP Promotes Osteoclast Fusion for Pathogenic Bone Resorption in Periodontitis via Upregulation of Permissive Fusogen CD9

Nova Southeastern University, Davie, Florida, USA

Objectives: Multinuclear osteoclasts (OC) resulting from fusion between OC precursors plays a key role in bone resorption. Several cell-surface fusogens are involved in osteoclast cell-fusion, such as, CD9, osteoclast-stimulatory transmembrane protein (OC-STAMP) and dendritic cell-specific transmembrane protein (DC-STAMP). The object of this study was to elucidate the role of OC-STAMP in the OC-mediated pathogenic bone resorption using a mouse model of ligature-induced periodontitis. Methods: Effects of anti-OC-STAMP-neutralizing mAb on RANKL-induced osteoclastogenesis and cell fusion was monitored in vitro by TRAP-staining, while qPCR was performed for detection of CD9, OC-STAMP and DC-STAMP mRNAs. C57BL6/j mice that received ligature-attachment to the maxillary molar were treated with systemic administration of anti-OC-STAMP-mAb or control mAb, and level of periodontal bone loss and TRAP+ multinuclear OCs were monitored at Day-7. Results: Stimulation of mononuclear OC-precursors with RANKL in vitro induced cell fusion, whereas anti-OC-STAMP-neutralizing mAb down-modulated; 1) the emergence of large multinuclear TRAP+ OC cells, 2) pit formation and 3) mRNA and protein expression of CD9, but not DC-STAMP, in RANKL-stimulated OC-precursors. While anti-DC-STAMP-mAb also downregulated RANKL-induced osteoclastogenesis in vitro, it had no effect on CD9 expression. Systemic administration of anti-OC-STAMP-mAb to ligature-received mice, compared to control mAb, suppressed the alveolar bone loss along with the diminished expression of CD9 mRNA and reduced emergence TRAP+ multinuclear osteoclasts. Conclusions: The present study demonstrated that OC-STAMP is engaged in pathogenic periodontal bone loss via upregulation of OC cell-fusion by upregulation of permissive fusogen CD9, but not DC-STAMP, suggesting that OC-STAMP/CD9 axis induces periodontal bone loss.