Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Mar 4;18(4):589-94.
doi: 10.1038/nm.2659.

Vitamin E decreases bone mass by stimulating osteoclast fusion

Koji Fujita  1 , 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
Affiliations

Vitamin E decreases bone mass by stimulating osteoclast fusion

Koji Fujita et al. Nat Med. .

Erratum in

  • Nat Med. 2012 Sep;18(9):1445

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.

PubMed Disclaimer

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. J Bone Miner Metab. 2010 Sep;28(5):503-9 - PubMed
    1. Annu Rev Cell Dev Biol. 2009;25:629-48 - PubMed
    1. Biochem Biophys Res Commun. 2005 Oct 7;335(4):1239-46 - PubMed
    1. Ann Intern Med. 2005 Jan 4;142(1):37-46 - PubMed
    1. J Bone Miner Metab. 2003;21(6):323-36 - PubMed

Publication types

MeSH terms

LinkOut - more resources