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

Takenobu Ishii, Montserrat Ruiz-Torruella, Atsushi Ikeda, Satoru Shindo, Alexandru Movila, Hani Mawardi, Abdullah Albassam, Rayyan A. Kayal, Ayman A. Al-Dharrab, Kenji Egashira, Wichaya Wisitrasameewong, Kenta Yamamoto, Abdulghani I. Mira, Kenji Sueishi, Xiaozhe Han, Martin A. Taubman, Takeshi Miyamoto, Toshihisa Kawai

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4016-4030
Number of pages15
JournalFASEB Journal
Volume32
Issue number7
DOIs
Publication statusPublished - Jul 2018
Externally publishedYes

Keywords

  • DC-STAMP
  • Mouse model
  • Osteoclastogenesis
  • Periodontal bone loss
  • RANKL

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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