TY - JOUR
T1 - OC-STAMP promotes osteoclast fusion for pathogenic bone resorption in periodontitis via up-regulation of permissive fusogen CD9
AU - Ishii, Takenobu
AU - Ruiz-Torruella, Montserrat
AU - Ikeda, Atsushi
AU - Shindo, Satoru
AU - Movila, Alexandru
AU - Mawardi, Hani
AU - Albassam, Abdullah
AU - Kayal, Rayyan A.
AU - Al-Dharrab, Ayman A.
AU - Egashira, Kenji
AU - Wisitrasameewong, Wichaya
AU - Yamamoto, Kenta
AU - Mira, Abdulghani I.
AU - Sueishi, Kenji
AU - Han, Xiaozhe
AU - Taubman, Martin A.
AU - Miyamoto, Takeshi
AU - Kawai, Toshihisa
N1 - Funding Information:
This work was supported, in part, by U.S. National Institutes of Health (NIH) National Institute of Dental and Craniofacial Research Grants DE-018499, DE-019917, and T32 DE 007327-12, NIH National Institute on Aging Grant AG-053615, and a research grant from King Abdulaziz University. The authors declare no conflicts of interest.
Publisher Copyright:
© FASEB.
PY - 2018/7
Y1 - 2018/7
N2 - 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-kB 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.
AB - 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-kB 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.
KW - DC-STAMP
KW - Mouse model
KW - Osteoclastogenesis
KW - Periodontal bone loss
KW - RANKL
UR - http://www.scopus.com/inward/record.url?scp=85049254204&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049254204&partnerID=8YFLogxK
U2 - 10.1096/fj.201701424R
DO - 10.1096/fj.201701424R
M3 - Article
C2 - 29533736
AN - SCOPUS:85049254204
SN - 0892-6638
VL - 32
SP - 4016
EP - 4030
JO - FASEB Journal
JF - FASEB Journal
IS - 7
ER -