Presentation Title

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

Speaker Credentials

Professor

Speaker Credentials

Ph.D.

College

College of Dental Medicine

Location

Nova Southeastern University, Davie, Florida, USA

Format

Podium Presentation

Start Date

16-2-2018 11:15 AM

End Date

16-2-2018 11:45 AM

Abstract

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.

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Feb 16th, 11:15 AM Feb 16th, 11:45 AM

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.