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.
journal_name
Nat Medjournal_title
Nature medicineauthors
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 Sdoi
10.1038/nm.2659subject
Has Abstractpub_date
2012-03-04 00:00:00pages
589-94issue
4eissn
1078-8956issn
1546-170Xpii
nm.2659journal_volume
18pub_type
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