| Autor: |
Ishii T; Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, Massachusetts, USA.; Orthodontics, Tokyo Dental College, Tokyo, Japan., Ruiz-Torruella M; Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, Massachusetts, USA., Ikeda A; Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, Massachusetts, USA., Shindo S; Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, Massachusetts, USA., Movila A; Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, Massachusetts, USA., Mawardi H; Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia., Albassam A; Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia., Kayal RA; Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia., Al-Dharrab AA; Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia., Egashira K; Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, Massachusetts, USA.; Research and Development Headquarters, Lion Corporation, Odawara, Japan., Wisitrasameewong W; Periodontology, Chulalongkorn University, Bangkok, Thailand., Yamamoto K; Department of Periodontology, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, Florida, USA., Mira AI; Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia., Sueishi K; Orthodontics, Tokyo Dental College, Tokyo, Japan., Han X; Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, Massachusetts, USA.; Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA., Taubman MA; Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, Massachusetts, USA.; Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, USA., Miyamoto T; Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan; and., Kawai T; Department of Periodontology, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, Florida, USA. |
| Abstrakt: |
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 transmembrane protein (DC-STAMP)], and permissive fusogen CD9, are involved in OC fusion. In contrast to DC-STAMP-knockout (KO) mice, which show the osteopetrotic phenotype, OC-STAMP-KO mice show no difference in systemic bone mineral density. Nonetheless, according to the ligature-induced periodontitis model, significantly lower level of bone resorption was found in OC-STAMP-KO mice compared to WT mice. Anti-OC-STAMP-neutralizing mAb down-modulated in vitro: 1) the emergence of large multinuclear tartrate-resistant acid phosphatase-positive cells, 2) pit formation, and 3) mRNA and protein expression of CD9, but not DC-STAMP, in receptor activator of NF-κB ligand (RANKL)-stimulated OC precursor cells (OCps). While anti-DC-STAMP-mAb also down-regulated RANKL-induced osteoclastogenesis in vitro, it had no effect on CD9 expression. In our mouse model, systemic administration of anti-OC-STAMP-mAb suppressed the expression of CD9 mRNA, but not DC-STAMP mRNA, in periodontal tissue, along with diminished alveolar bone loss and reduced emergence of CD9 + OCps and tartrate-resistant acid phosphatase-positive multinuclear OCs. The present study demonstrated that OC-STAMP partners CD9 to promote periodontal bone destruction by up-regulation of fusion during osteoclastogenesis, suggesting that anti-OC-STAMP-mAb may lead to the development of a novel therapeutic regimen for periodontitis.-Ishii, T., Ruiz-Torruella, M., Ikeda, A., Shindo, S., Movila, A., Mawardi, H., Albassam, A., Kayal, R. A., Al-Dharrab, A. A., Egashira, K., Wisitrasameewong, W., Yamamoto, K., Mira, A. I., Sueishi, K., Han, X., Taubman, M. A., Miyamoto, T., Kawai, T. OC-STAMP promotes osteoclast fusion for pathogenic bone resorption in periodontitis via up-regulation of permissive fusogen CD9. |
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