OC‐STAMP promotes osteoclast fusion for pathogenic bone resorption in periodontitis via up‐regulation of permissive fusogen CD9

• DOI: 10.1096/fj.201701424r
• Publication Date: 2018-03-13T21:19:03Z
• Authors: Takenobu Ishii; Montserrat Ruiz‐T...; Atsushi Ikeda; Satoru Shindo; Alexandru Movila; Hani Mawardi; Abdullah Albassam; Rayyan A. Kayal; Ayman A. Al‐Dharrab; Kenji Egashira; Wichaya Wisitrasa...; Kenta Yamamoto; Abdulghani I. Mira; Kenji Sueishi; Xiaozhe Han; Martin A. Taubman; Takeshi Miyamoto; Toshihisa Kawai
• Keywords: Permissive

Cell fusion-mediated formation of multinuclear osteoclasts (OCs) plays a key role in bone resorption. It is reported that 2 unique OC-specific fusogens [i.e., OC-stimulatory transmembrane protein (OC-STAMP) and dendritic cell–specific (DC-STAMP)], permissive fusogen CD9, are involved OC fusion. In contrast to DC-STAMP-knockout (KO) mice, which show the osteopetrotic phenotype, OC-STAMP-KO mice no difference systemic mineral density. Nonetheless, according ligature-induced periodontitis model, significantly lower level resorption was found compared WT mice. Anti-OC-STAMP-neutralizing mAb down-modulated vitro: 1) emergence large tartrate- resistant acid phosphatase-positive cells, 2) pit formation, 3) mRNA expression but not DC-STAMP, receptor activator NF-κB ligand (RANKL)-stimulated precursor cells (OCps). While anti–DC-STAMP-mAb also down-regulated RANKL-induced osteoclastogenesis vitro, it had effect on CD9 expression. our mouse administration anti–OC-STAMP-mAb suppressed mRNA, DC-STAMP periodontal tissue, along with diminished alveolar loss reduced CD9+ OCps tartrate-resistant OCs. The present study demonstrated OC-STAMP partners promote destruction by up-regulation fusion during osteoclastogenesis, suggesting may lead development novel therapeutic regimen for periodontitis.—Ishii, T., Ruiz-Torruella, M., Ikeda, A., Shindo, S., Movila, Mawardi, H., Albassam, Kayal, R. Al-Dharrab, A. Egashira, K., Wisitrasameewong, W., Yamamoto, Mira, I., Sueishi, Han, X., Taubman, M. Miyamoto, Kawai, T. promotes osteoclast pathogenic via CD9. FASEB J. 32, 4016–4030 (2018). www.fasebj.org