Title: 0126 - Engagement of OC-STAMP in Pathogenic Periodontal Bone-resorption Via CD9-mediated Osteoclast-fusion
Toshihisa Kawai (Presenter)
Nova Southeastern University
Takenobu Ishii, Tokyo Dental College
Kenta Yamamoto, Nova Southeastern University
Atsushi Ikeda, Ohio State University
Satoru Shindo, Hiroshima University
Alexandru Movila, Nova Southeastern University
Saynur Vardar-Sengul, Nova Southeastern University
Maria Hernandez, nova southeastern university
Objectives: Cell-fusion-mediated formation of multinuclear osteoclasts (OC) plays a key role in bone resorption processes. 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). Herein, we investigated a possible role of OC-STAMP which is distinctively expressed by OC in periodontal bone resorption using a mouse model of ligature-induced periodontitis.
Methods: Effects of anti-OC-STAMP-neutralizing mAb as well as anti-DC-STAMP-neutralizing mAb on RANKL-induced osteoclastogenesis in vitro was monitored by TRAP-staining, pit formation assay, while qPCR was performed for detections of CD9, OC-STAMP and DC-STAMP mRNAs. The level of cell-fusion was evaluated by the emergence of multi-nuclear OC. C57BL6/j mice (6-8w old male, n=6/group) that received ligature-attachment to the maxillary molar were treated with systemic administration of anti-OC-STAMP-mAb or control mAb. Level of periodontal bone loss, mRNAs for CD9 and DC-STAMP and TRAP+ multinuclear OCs were monitored at Day-7.
Results: Transient expression of OC-STAMP was observed in mononuclear OC-precursors 2-3 days after RANKL stimulation, whereas anti-OC-STAMP-neutralizing mAb down-modulated: 1) the emergence of large multinuclear TRAP+ 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. Nonetheless, anti-CD9-mAb-mediated suppression of osteoclastogenesis was further promoted by anti-DC-STAMP-mAb, but not by anti-OC-STAMP-mAb. Systemic administration of anti-OC-STAMP-mAb to ligature-received mice, compared to control mAb, suppressed the expression of CD9 mRNA (P<0.01), but not DC-STAMP mRNA, in the periodontal tissue, along with diminished alveolar bone loss (P<0.05) and reduced emergence TRAP+ multinuclear osteoclasts (P<0.05).
Conclusions: The present study demonstrated that OC-STAMP is engaged in pathogenic periodontal bone destruction via upregulation of OC cell-fusion involving CD9, but not DC-STAMP, suggesting that OC-STAMP/CD9 axis induces periodontal bone loss in a manner independent of DC-STAMP.
This abstract is based on research that was funded entirely or partially by an outside source:
NIH grants DE-018499, DE-019917
The submitter must disclose the names of the organizations with which any author have a relationship, the nature of the relationship, and the clinical or research area involved. The following is submitted: NONE