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

研究成果: Article

113 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)589-594
ページ数6
ジャーナルNature Medicine
18
発行部数4
DOI
出版物ステータスPublished - 2012 4

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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)

これを引用

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.

:: Nature Medicine, 巻 18, 番号 4, 04.2012, p. 589-594.

研究成果: Article

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, 巻. 18, 番号 4, pp. 589-594. https://doi.org/10.1038/nm.2659
Fujita K, Iwasaki M, Ochi H, Fukuda T, Ma C, Miyamoto T その他. Vitamin E decreases bone mass by stimulating osteoclast fusion. Nature Medicine. 2012 4;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. :: Nature Medicine. 2012 ; 巻 18, 番号 4. pp. 589-594.
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