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Vitamin E decreases bone mass by stimulating osteoclast fusion

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,... Full description

Journal Title: Nature medicine 2012-03-04, Vol.18 (4), p.589-594
Main Author: Fujita, Koji
Other Authors: 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
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: United States: Nature Publishing Group
ID: ISSN: 1078-8956
Link: https://www.ncbi.nlm.nih.gov/pubmed/22388090
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recordid: cdi_gale_infotracacademiconefile_A287113138
title: Vitamin E decreases bone mass by stimulating osteoclast fusion
format: Article
creator:
  • 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
subjects:
  • alpha-Tocopherol - administration & dosage
  • alpha-Tocopherol - blood
  • Amino Acids - blood
  • Animals
  • Apoptosis - drug effects
  • Bone and Bones - diagnostic imaging
  • Bone and Bones - drug effects
  • Bone and Bones - pathology
  • Bone density
  • Bone Resorption - diet therapy
  • Bone Resorption - etiology
  • Bone Resorption - genetics
  • Bones
  • Bromodeoxyuridine - metabolism
  • Carrier Proteins - genetics
  • Cell Differentiation - drug effects
  • Cell Proliferation - drug effects
  • Cells, Cultured
  • Cellular biology
  • Chromatin Immunoprecipitation
  • Density
  • Dietary supplements
  • Disease Models, Animal
  • Gene expression
  • Gene Expression Regulation - drug effects
  • Genetic aspects
  • Humans
  • In Situ Nick-End Labeling
  • Macrophage Colony-Stimulating Factor - metabolism
  • Membrane Proteins - deficiency
  • Membrane Proteins - genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microphthalmia-Associated Transcription Factor - metabolism
  • Mitogen-Activated Protein Kinase 14 - metabolism
  • Nitrophenols - metabolism
  • Osteoblasts
  • Osteoclasts - drug effects
  • Osteocytes - drug effects
  • Osteocytes - metabolism
  • Physiological aspects
  • Proteins
  • RANK Ligand - metabolism
  • Rats
  • Research
  • RNA, Small Interfering - pharmacology
  • Signal Transduction - drug effects
  • Signal Transduction - genetics
  • Tomography, X-Ray Computed
  • Transfection
  • Vitamin E
  • Vitamin E - administration & dosage
  • Vitamin E - blood
  • Vitamin E Deficiency - complications
  • Vitamin E Deficiency - diet therapy
  • Vitamin E Deficiency - genetics
  • Vitamin E Deficiency - pathology
  • Vitamins - administration & dosage
  • Vitamins - blood
ispartof: Nature medicine, 2012-03-04, Vol.18 (4), p.589-594
description: 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.
language: eng
source:
identifier: ISSN: 1078-8956
fulltext: no_fulltext
issn:
  • 1078-8956
  • 1546-170X
url: Link


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titleVitamin E decreases bone mass by stimulating osteoclast fusion
creatorFujita, 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
creatorcontribFujita, 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
descriptionBone 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.
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subjectalpha-Tocopherol - administration & dosage ; alpha-Tocopherol - blood ; Amino Acids - blood ; Animals ; Apoptosis - drug effects ; Bone and Bones - diagnostic imaging ; Bone and Bones - drug effects ; Bone and Bones - pathology ; Bone density ; Bone Resorption - diet therapy ; Bone Resorption - etiology ; Bone Resorption - genetics ; Bones ; Bromodeoxyuridine - metabolism ; Carrier Proteins - genetics ; Cell Differentiation - drug effects ; Cell Proliferation - drug effects ; Cells, Cultured ; Cellular biology ; Chromatin Immunoprecipitation ; Density ; Dietary supplements ; Disease Models, Animal ; Gene expression ; Gene Expression Regulation - drug effects ; Genetic aspects ; Humans ; In Situ Nick-End Labeling ; Macrophage Colony-Stimulating Factor - metabolism ; Membrane Proteins - deficiency ; Membrane Proteins - genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microphthalmia-Associated Transcription Factor - metabolism ; Mitogen-Activated Protein Kinase 14 - metabolism ; Nitrophenols - metabolism ; Osteoblasts ; Osteoclasts - drug effects ; Osteocytes - drug effects ; Osteocytes - metabolism ; Physiological aspects ; Proteins ; RANK Ligand - metabolism ; Rats ; Research ; RNA, Small Interfering - pharmacology ; Signal Transduction - drug effects ; Signal Transduction - genetics ; Tomography, X-Ray Computed ; Transfection ; Vitamin E ; Vitamin E - administration & dosage ; Vitamin E - blood ; Vitamin E Deficiency - complications ; Vitamin E Deficiency - diet therapy ; Vitamin E Deficiency - genetics ; Vitamin E Deficiency - pathology ; Vitamins - administration & dosage ; Vitamins - blood
ispartofNature medicine, 2012-03-04, Vol.18 (4), p.589-594
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1Iwasaki, Makiko
2Ochi, Hiroki
3Fukuda, Toru
4Ma, Chengshan
5Miyamoto, Takeshi
6Takitani, Kimitaka
7Negishi-Koga, Takako
8Sunamura, Satoko
9Kodama, Tatsuhiko
10Takayanagi, Hiroshi
11Tamai, Hiroshi
12Kato, Shigeaki
13Arai, Hiroyuki
14Shinomiya, Kenichi
15Itoh, Hiroshi
16Okawa, Atsushi
17Takeda, Shu
title
0Vitamin E decreases bone mass by stimulating osteoclast fusion
1Nature medicine
addtitleNat Med
descriptionBone 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.
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1alpha-Tocopherol - blood
2Amino Acids - blood
3Animals
4Apoptosis - drug effects
5Bone and Bones - diagnostic imaging
6Bone and Bones - drug effects
7Bone and Bones - pathology
8Bone density
9Bone Resorption - diet therapy
10Bone Resorption - etiology
11Bone Resorption - genetics
12Bones
13Bromodeoxyuridine - metabolism
14Carrier Proteins - genetics
15Cell Differentiation - drug effects
16Cell Proliferation - drug effects
17Cells, Cultured
18Cellular biology
19Chromatin Immunoprecipitation
20Density
21Dietary supplements
22Disease Models, Animal
23Gene expression
24Gene Expression Regulation - drug effects
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26Humans
27In Situ Nick-End Labeling
28Macrophage Colony-Stimulating Factor - metabolism
29Membrane Proteins - deficiency
30Membrane Proteins - genetics
31Mice
32Mice, Inbred C57BL
33Mice, Knockout
34Microphthalmia-Associated Transcription Factor - metabolism
35Mitogen-Activated Protein Kinase 14 - metabolism
36Nitrophenols - metabolism
37Osteoblasts
38Osteoclasts - drug effects
39Osteocytes - drug effects
40Osteocytes - metabolism
41Physiological aspects
42Proteins
43RANK Ligand - metabolism
44Rats
45Research
46RNA, Small Interfering - pharmacology
47Signal Transduction - drug effects
48Signal Transduction - genetics
49Tomography, X-Ray Computed
50Transfection
51Vitamin E
52Vitamin E - administration & dosage
53Vitamin E - blood
54Vitamin E Deficiency - complications
55Vitamin E Deficiency - diet therapy
56Vitamin E Deficiency - genetics
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58Vitamins - administration & dosage
59Vitamins - blood
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12Kato, Shigeaki
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titleVitamin E decreases bone mass by stimulating osteoclast fusion
authorFujita, 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
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3Animals
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5Bone and Bones - diagnostic imaging
6Bone and Bones - drug effects
7Bone and Bones - pathology
8Bone density
9Bone Resorption - diet therapy
10Bone Resorption - etiology
11Bone Resorption - genetics
12Bones
13Bromodeoxyuridine - metabolism
14Carrier Proteins - genetics
15Cell Differentiation - drug effects
16Cell Proliferation - drug effects
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20Density
21Dietary supplements
22Disease Models, Animal
23Gene expression
24Gene Expression Regulation - drug effects
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28Macrophage Colony-Stimulating Factor - metabolism
29Membrane Proteins - deficiency
30Membrane Proteins - genetics
31Mice
32Mice, Inbred C57BL
33Mice, Knockout
34Microphthalmia-Associated Transcription Factor - metabolism
35Mitogen-Activated Protein Kinase 14 - metabolism
36Nitrophenols - metabolism
37Osteoblasts
38Osteoclasts - drug effects
39Osteocytes - drug effects
40Osteocytes - metabolism
41Physiological aspects
42Proteins
43RANK Ligand - metabolism
44Rats
45Research
46RNA, Small Interfering - pharmacology
47Signal Transduction - drug effects
48Signal Transduction - genetics
49Tomography, X-Ray Computed
50Transfection
51Vitamin E
52Vitamin E - administration & dosage
53Vitamin E - blood
54Vitamin E Deficiency - complications
55Vitamin E Deficiency - diet therapy
56Vitamin E Deficiency - genetics
57Vitamin E Deficiency - pathology
58Vitamins - administration & dosage
59Vitamins - blood
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8Sunamura, Satoko
9Kodama, Tatsuhiko
10Takayanagi, Hiroshi
11Tamai, Hiroshi
12Kato, Shigeaki
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14Shinomiya, Kenichi
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7Negishi-Koga, Takako
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abstractBone 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.
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pmid22388090
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