Vitamin E decreases bone mass by stimulating osteoclast fusion

Koji Fujita, Makiko Iwasaki, Hiroki Ochi, Toru Fukuda, Chengshan Ma, Takeshi Miyamoto, Kimitaka Takitani, Takako Negishi-Koga, Satoko Sunamura, Tatsuhiko Kodama, Hiroshi Takayanagi, Hiroshi Tamai, Shigeaki Kato, Hiroyuki Arai, Kenichi Shinomiya, Hiroshi Itoh, Atsushi Okawa, Shu Takeda

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption. Osteoclasts are multinucleated cells that are formed by mononuclear preosteoclast fusion. Fat-soluble vitamins such as vitamin D are pivotal in maintaining skeletal integrity. However, the role of vitamin E in bone remodeling is unknown. Here, we show that mice deficient in α-tocopherol transfer protein (Ttpa -/- mice), a mouse model of genetic vitamin E deficiency, have high bone mass as a result of a decrease in bone resorption. Cell-based assays indicated that α-tocopherol stimulated osteoclast fusion, independent of its antioxidant capacity, by inducing the expression of dendritic-cell-specific transmembrane protein, an essential molecule for osteoclast fusion, through activation of mitogen-activated protein kinase 14 (p38) and microphthalmia-associated transcription factor, as well as its direct recruitment to the Tm7sf4 (a gene encoding DC-STAMP) promoter. Indeed, the bone abnormality seen in Ttpa -/- mice was rescued by a Tm7sf4 transgene. Moreover, wild-type mice or rats fed an α-tocopherol- supplemented diet, which contains a comparable amount of α-tocopherol to supplements consumed by many people, lost bone mass. These results show that serum vitamin E is a determinant of bone mass through its regulation of osteoclast fusion.

Original languageEnglish
Pages (from-to)589-594
Number of pages6
JournalNature Medicine
Volume18
Issue number4
DOIs
Publication statusPublished - 2012 Apr

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Osteoclasts
Vitamin E
Tocopherols
Bone
Fusion reactions
Bone and Bones
Bone Resorption
Mitogen-Activated Protein Kinase 14
Microphthalmia-Associated Transcription Factor
Vitamin E Deficiency
Bone Remodeling
Genetic Models
p38 Mitogen-Activated Protein Kinases
Transgenes
Osteogenesis
Vitamin D
Vitamins
Dendritic Cells
Homeostasis
Antioxidants

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Fujita, K., Iwasaki, M., Ochi, H., Fukuda, T., Ma, C., Miyamoto, T., ... Takeda, S. (2012). Vitamin E decreases bone mass by stimulating osteoclast fusion. Nature Medicine, 18(4), 589-594. https://doi.org/10.1038/nm.2659

Vitamin E decreases bone mass by stimulating osteoclast fusion. / Fujita, Koji; Iwasaki, Makiko; Ochi, Hiroki; Fukuda, Toru; Ma, Chengshan; Miyamoto, Takeshi; Takitani, Kimitaka; Negishi-Koga, Takako; Sunamura, Satoko; Kodama, Tatsuhiko; Takayanagi, Hiroshi; Tamai, Hiroshi; Kato, Shigeaki; Arai, Hiroyuki; Shinomiya, Kenichi; Itoh, Hiroshi; Okawa, Atsushi; Takeda, Shu.

In: Nature Medicine, Vol. 18, No. 4, 04.2012, p. 589-594.

Research output: Contribution to journalArticle

Fujita, K, Iwasaki, M, Ochi, H, Fukuda, T, Ma, C, Miyamoto, T, Takitani, K, Negishi-Koga, T, Sunamura, S, Kodama, T, Takayanagi, H, Tamai, H, Kato, S, Arai, H, Shinomiya, K, Itoh, H, Okawa, A & Takeda, S 2012, 'Vitamin E decreases bone mass by stimulating osteoclast fusion', Nature Medicine, vol. 18, no. 4, pp. 589-594. https://doi.org/10.1038/nm.2659
Fujita K, Iwasaki M, Ochi H, Fukuda T, Ma C, Miyamoto T et al. Vitamin E decreases bone mass by stimulating osteoclast fusion. Nature Medicine. 2012 Apr;18(4):589-594. https://doi.org/10.1038/nm.2659
Fujita, Koji ; Iwasaki, Makiko ; Ochi, Hiroki ; Fukuda, Toru ; Ma, Chengshan ; Miyamoto, Takeshi ; Takitani, Kimitaka ; Negishi-Koga, Takako ; Sunamura, Satoko ; Kodama, Tatsuhiko ; Takayanagi, Hiroshi ; Tamai, Hiroshi ; Kato, Shigeaki ; Arai, Hiroyuki ; Shinomiya, Kenichi ; Itoh, Hiroshi ; Okawa, Atsushi ; Takeda, Shu. / Vitamin E decreases bone mass by stimulating osteoclast fusion. In: Nature Medicine. 2012 ; Vol. 18, No. 4. pp. 589-594.
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