Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. Signal., 10 April 2012
Vol. 5, Issue 219, p. ec104
[DOI: 10.1126/scisignal.2003117]

EDITORS' CHOICE

Bone Break a Bone

Wei Wong

Science Signaling, AAAS, Washington, DC 20005, USA

Vitamin E is a lipid-soluble antioxidant that is predominantly biologically available as α-tocopherol. Vitamin E supplements are frequently consumed because of their reported beneficial effects on the cardiovascular system (see Roodman); however, different studies have shown beneficial or deleterious effects on bone homeostasis. Ttpa–/– mice are a genetic model for vitamin E deficiency because they lack α-tocopherol transfer protein (α-TTP), a liver protein that helps to recycle α-tocopherol from plasma. Fujita et al. found that, compared with wild-type mice, Ttpa–/– mice had greater bone mass because of lower bone resorption, rather than increased bone formation. Treatment of bone marrow cells from wild-type mice with α-tocopherol increased their differentiation into osteoclasts (cells that mediate bone resorption) without affecting their differentiation into osteoblasts (cells that mediate bone formation). α-tocopherol promoted osteoclast fusion (which occurs late in osteoclast maturation), an effect that was mediated by increased expression of the gene encoding dendritic-cell–specific transmembrane protein (DC-STAMP), a receptor that is required for osteoclast fusion, rather than the antioxidant properties of α-tocopherol. Treatment of bone marrow cells with α-tocopherol activated the mitogen-activated protein kinase (MAPK) p38α and its upstream kinases mitogen-activated protein kinase kinases 3 and 6 (MKK3/6). p38α phosphorylated and activated microphthalmia-associated transcription factor (MITF), which is required for osteoclast development and bound to the promoter of the gene encoding DC-STAMP. Wild-type mice that received α-tocopherol at concentrations comparable to those in human dietary supplements showed decreased bone mass, which correlated with increased bone resorption and osteoclast size. Thus, individuals who consume vitamin E supplements could be at increased risk for bone loss.

K. Fujita, M. Iwasaki, H. Ochi, T. Fukuda, C. Ma, T. Miyamoto, K. Takitani, T. Negishi-Koga, S. Sunamura, T. Kodama, H. Takayanagi, H. Tamai, S. Kato, H. Arai, K. Shinomiya, H. Itoh, A. Okawa, S. Takeda, Vitamin E decreases bone mass by stimulating osteoclast fusion. Nat. Med. 18, 589–594 (2012). [Online Journal]

G. D. Roodman, Vitamin E: Good for the heart, bad for the bones? Nat. Med. 18, 491–492 (2012). [Online Journal]

Citation: W. Wong, Break a Bone. Sci. Signal. 5, ec104 (2012).



To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882