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Web of Knowledge Page 1 (Records 1 -- 1) [1] Record 1 of 1 Title: Aldehyde-stress resulting from Aldh2 mutation promotes osteoporosis due to impaired osteoblastogenesis Author(s): Hoshi, H (Hoshi, Hiroko); Hao, W (Hao, Wu); Fujita, Y (Fujita, Yoshinari); Funayama, A (Funayama, Atsushi); Miyauchi, Y (Miyauchi, Yoshiteru); Hashimoto, K (Hashimoto, Kazuaki); Miyamoto, K (Miyamoto, Kana); Iwasaki, R (Iwasaki, Ryotaro); Sato, Y (Sato, Yuiko); Kobayashi, T (Kobayashi, Tami); Miyamoto, H (Miyamoto, Hiroya); Yoshida, S (Yoshida, Shigeyuki); Mori, T (Mori, Tomoaki); Kanagawa, H (Kanagawa, Hiroya); Katsuyama, E (Katsuyama, Eri); Fujie, A (Fujie, Atsuhiro); Kitagawa, K (Kitagawa, Kyoko); Nakayama, KI (Nakayama, Keiichi I.); Kawamoto, T (Kawamoto, Toshihiro); Sano, M (Sano, Motoaki); Fukuda, K (Fukuda, Keiichi); Ohsawa, I (Ohsawa, Ikuroh); Ohta, S (Ohta, Shigeo); Morioka, H (Morioka, Hideo); Matsumoto, M (Matsumoto, Morio); Chiba, K (Chiba, Kazuhiro); Toyama, Y (Toyama, Yoshiaki); Miyamoto, T (Miyamoto, Takeshi) Source: JOURNAL OF BONE AND MINERAL RESEARCH Volume: 27 Issue: 9 Pages: 2015-2023 DOI: 10.1002/jbmr.1634 Published: SEP 2012 Times Cited in Web of Science: 0 Total Times Cited: 0 Cited Reference Count: 39 Abstract: Osteoporosis is a complex disease with various causes, such as estrogen loss, genetics, and aging. Here we show that a dominant-negative form of aldehyde dehydrogenase 2 (ALDH2) protein, ALDH2*2, which is produced by a single nucleotide polymorphism (rs671), promotes osteoporosis due to impaired osteoblastogenesis. Aldh2 plays a role in alcohol-detoxification by acetaldehyde-detoxification; however, transgenic mice expressing Aldh2*2 (Aldh2*2 Tg) exhibited severe osteoporosis with increased levels of blood acetaldehyde without alcohol consumption, indicating that Aldh2 regulates physiological bone homeostasis. Wild-type osteoblast differentiation was severely inhibited by exogenous acetaldehyde, and osteoblastic markers such as osteocalcin, runx2, and osterix expression, or phosphorylation of Smad1,5,8 induced by bone morphogenetic protein 2 (BMP2) was strongly altered by acetaldehyde. Acetaldehyde treatment also inhibits proliferation and induces apoptosis in osteoblasts. The Aldh2*2 transgene or acetaldehyde treatment induced accumulation of the lipid-oxidant 4-hydroxy-2-nonenal (4HNE) and expression of peroxisome proliferatoractivated receptor gamma (PPAR?), a transcription factor that promotes adipogenesis and inhibits osteoblastogenesis. Antioxidant treatment inhibited acetaldehyde-induced proliferation-loss, apoptosis, and PPAR? expression and restored osteoblastogenesis inhibited by acetaldehyde. Treatment with a PPAR? inhibitor also restored acetaldehyde-mediated osteoblastogenesis inhibition. These results provide new insight into regulation of osteoporosis in a subset of individuals with ALDH2*2 and in alcoholic patients and suggest a novel strategy to promote bone formation in such osteopenic diseases. (c) 2012 American Society for Bone and Mineral Research. Accession Number: WOS:000307889000018 Language: English Document Type: Article Author Keywords: ALDEHYDE DEHYDROGENASE 2; OSTEOPOROSIS; ACETALDEHYDE; 4-HYDROXY-2NONENAL; OSTEOBLASTS KeyWords Plus: JAPANESE POPULATION; DEHYDROGENASE INCREASES; OXIDATIVE STRESS; GENE FAMILY; LIFE-STYLE; VITAMIN-E; DEFICIENCY; METABOLISM; ALCOHOL; DIFFERENTIATION Addresses: [Miyamoto, Takeshi] Keio Univ, Sch Med, Dept Orthoped Surg, Shinjuku Ku, Tokyo 1608582, Japan [Hoshi, Hiroko; Miyauchi, Yoshiteru; Miyamoto, Hiroya; Yoshida, Shigeyuki; Mori, Tomoaki; Katsuyama, Eri; Fujie, Atsuhiro; Miyamoto, Takeshi] Keio Univ, Sch Med, Ctr Human Metabol Syst Biol, Tokyo 1608582, Japan [Hashimoto, Kazuaki] Keio Univ, Sch Med, Dept Adv Therapy Spine & Spinal Cord Disorders, Tokyo 1608582, Japan [Miyamoto, Kana; Kobayashi, Tami; Miyamoto, Takeshi] Keio Univ, Sch Med, Keio Kanrinmaru Project, Tokyo 1608582, Japan [Iwasaki, Ryotaro; Yoshida, Shigeyuki] Keio Univ, Sch Med, Dept Dent & Oral Surg, Tokyo 1608582, Japan
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[Miyamoto, Takeshi] Keio Univ, Sch Med, Dept Integrated Bone Metab & Immunol, Tokyo 1608582, Japan [Kitagawa, Kyoko] Hamamatsu Univ Sch Med, Dept Biochem 1, Shizuoka, Japan [Nakayama, Keiichi I.] Kyushu Univ, Med Inst Bioregulat, Dept Mol & Cellular Biol, Fukuoka 812, Japan [Kawamoto, Toshihiro] Univ Occupat & Environm Hlth, Dept Environm Hlth, Kitakyushu, Fukuoka 807, Japan [Sano, Motoaki; Fukuda, Keiichi] Keio Univ, Sch Med, Dept Cardiol, Tokyo 1608582, Japan [Ohsawa, Ikuroh] Tokyo Metropolitan Inst Gerontol, Tokyo, Japan [Ohta, Shigeo] Nippon Med Sch, Grad Sch Med, Inst Dev & Aging Sci, Dept Biochem & Cell Biol, Kawasaki, Kanagawa, Japan Reprint Address: Miyamoto, T (reprint author), Keio Univ, Sch Med, Dept Orthoped Surg, Shinjuku Ku, 35 Shinano Machi, Tokyo 1608582, Japan. E-mail Address: miyamoto@z5.keio.jp Publisher: WILEY-BLACKWELL Publisher Address: 111 RIVER ST, HOBOKEN 07030-5774, NJ USA Web of Science Categories: Endocrinology & Metabolism Research Areas: Endocrinology & Metabolism IDS Number: 993VV ISSN: 0884-0431 29-char Source Abbrev.: J BONE MINER RES ISO Source Abbrev.: J. Bone Miner. Res. Source Item Page Count: 9 Funding: Funding Agency
Precursory Research for Embryonic Science and Technology (PREST) Takeda Science Foundation Inamori Foundation Keio Kanrinmaru project, Japan Asahi Breweries Foundation

Grant Number

We thank Prof. H. Matsuhashi at Hokkaido University of Education for technical support of gas-liquid chromatography analysis. T. Miyamoto was supported by a grant-in-aid for Young Scientists (A) and by Precursory Research for Embryonic Science and Technology (PREST), the Takeda Science Foundation, the Inamori Foundation and the Keio Kanrinmaru project, Japan. H. Hoshi was supported by a grant-in-aid for Young Scientists and by the Asahi Breweries Foundation. Web of Knowledge Page 1 (Records 1 -- 1) [1]
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