Pathogenic mechanisms of the bone diseases caused by defect in chondroitin sulfate biosynthesis

• Project/Area Number: 23790066
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Hokkaido University
• Principal Investigator: MIZUMOTO Shuji 北海道大学, 大学院・先端生命科学研究院, 博士研究員 (40443973)
• Research Collaborator: SUGAHARA Kazuyuki 北海道大学, 大学院・先端生命科学研究院, 特任教授 (60154449) ; YAMADA Shuhei 名城大学, 薬学部, 教授 (70240017) ; IKEGAWA Shiro 理化学研究所, 骨関節疾患研究チーム, 主任研究員 (30272496) ; MATSUMOTO Naomichi 横浜市立大学, 医学研究科, 教授 (80325638) ; MIYAKE Noriko 横浜市立大学, 医学研究科, 准教授 (40523494) ; KOSHO Tomoki 信州大学, 医学部附属病院, 講師 (90276311) ; STEFAN Mundlos Institute of Medical Genetics, Charite University Medicine, Germany ; LIHADH Al-gazali United Arab Emirates University, UAE ; KATRIN Hoffmann Institute of Medical Genetics, Charite University Medicine, Germany ; ANDREAS Janecke Innsbruck Medical University, Austlia
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: コンドロイチン硫酸/デルマタン硫酸/骨 / 皮膚/遺伝病/脊椎骨端異形成症/ エーラス / ダンロス症候群/糖転移酵素/硫酸基転移酵素 / コンドロイチン硫酸 / デルマタン硫酸 / プロテオグリカン / 骨形成 / 遺伝病 / グリコサミノグリカン / 変形性関節症 / ドイツ / ニュージーランド

Research Abstract

We have identified mutations in the genes encoding biosynthetic enzymes, glycosyltransferases and sulfotransferases, of the chondroitin sulfate and dermatan sulfate. These mutations result in the disturbance of thier polysaccharides, and cause bone and skin disorders including Larsen syndrome, spondyloepimetaphyseal dysplasia, and Ehlers-Danlos syndrome.

Research Products

• [Journal Article] Loss of dermatan sulfate epimerase (DSE) function results in musculocontractural Ehlers-Danlos syndrome (2013)
  • Author(s): Thomas Muller, Shuji Mizumoto, Indrajit Suresh, Yoshie Komatsu, Julia Vodopiutz, Munis Dundar, Volker Straub, Arno Lingenhel, Andreas Melmer, Silvia Lechner, Johannes Zschocke, Kazuyuki Sugahara, Andreas R Janecke
  • Journal Title: Human Molecular Genetics Volume: 22 Issue: 18 Pages: 3761-3772
  • DOI: 10.1093/hmg/ddt227
  • Peer Reviewed
• [Journal Article] Mutations in B3GALT6 which Encodes a Glycosaminoglycan Linker Region Enzyme Cause a Spectrum of Skeletal and Connective Tissue Disorders (2013)
  • Author(s): Masahiro Nakajima, Shuji Mizumoto et al.
  • Journal Title: American Journal of Human Genetics Volume: in press Issue: 6 Pages: 927-934
  • DOI: 10.1016/j.ajhg.2013.04.003
  • Peer Reviewed
• [Journal Article] Expression of N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase involved in chondroitin sulfate synthesis is responsible for pulmonary metastasis (2013)
  • Author(s): Mizumoto, S., Watanabe, M., Yamada, S., and Sugahara, K.
  • Journal Title: BioMed Research International Volume: 2013 Pages: 656319-656319
  • DOI: 10.1155/2013/656319
  • NAID: 120005906914
  • Peer Reviewed
• [Journal Article] Interaction of chondroitin sulfate and dermatan sulfate from various biological sources with heparin-binding growth factors and cytokines (2013)
  • Author(s): Shuji Mizumoto, Duriya Fongmoon, Kazuyuki Sugahara
  • Journal Title: Glycoconjugate Journal Volume: in press Issue: 6 Pages: 619-632
  • DOI: 10.1007/s10719-012-9463-5
  • Peer Reviewed
• [Journal Article] Novel highly sulfated hexasaccharide sequences isolated from chondroitin sulfate of shark fin cartilage: Insights into the sugar sequences with bioactivities (2013)
  • Author(s): Shuji Mizumoto, Saori Murakoshi, Kittiwan Kalayanamitra, Sarama Sathyaseelan Deepa, Shigeyuki Fukui, Prachya Kongtawelert, Shuhei Yamada, and Kazuyuki Sugahara
  • Journal Title: Glycobiology Volume: 23 Issue: 2 Pages: 155-168
  • DOI: 10.1093/glycob/cws137
  • Peer Reviewed
• [Journal Article] Human genetic disorders caused by defective genes encoding biosynthetic enzymes for sulfated glycosaminoglycans (2013)
  • Author(s): Shuji Mizumoto, Shiro Ikegawa, andKazuyuki Sugahara
  • Journal Title: Journal of Biological Chemistry Volume: 288 Issue: 16 Pages: 10953-10961
  • DOI: 10.1074/jbc.r112.437038
  • Peer Reviewed
• [Journal Article] Reduction of Chondroitin 4-<i>O</i>-Sulfotransferase-1 Expression Causes Costello Syndrome (2013)
  • Author(s): Shuji Mizumoto
  • Journal Title: Trends in Glycoscience and Glycotechnology Volume: 25 Issue: 142 Pages: 87-89
  • DOI: 10.4052/tigg.25.87
  • NAID: 10031190623
  • ISSN: 0915-7352, 1883-2113
  • Peer Reviewed
• [Journal Article] Glycosaminoglycans are functional ligands for Receptor for Advanced Glycation End-products (RAGE) in tumors (2013)
  • Author(s): Mizumoto, S., and Sugahara, K.
  • Journal Title: FEBS Journal Volume: 280 Issue: 10 Pages: 2462-2470
  • DOI: 10.1111/febs.12156
  • Peer Reviewed
• [Journal Article] Receptor for Advanced Glycation End Products (RAGE) Functions as a Receptor for Specific Sulfated Glycosaminoglycans, and Anti-RAGE Antibody or The Sulfated Glycosaminoglycans Delivered in vivo Inhibit Pulmonary Metastasis of Tumor Cells (2012)
  • Author(s): Mizumoto, S., Takahashi, J., and Sugahara, K.
  • Journal Title: Journal of Biological Chemistry Volume: 287 Issue: 23 Pages: 18985-18994
  • DOI: 10.1074/jbc.m111.313437
  • Peer Reviewed
• [Journal Article] Glycosaminoglycan chain analysis and characterization (Glycosylation/Epimerization) (2012)
  • Author(s): Shuji Mizumoto and Kazuyuki Sugahara
  • Journal Title: Methods in Molecular Biology, (Proteoglycans: Methods and Protocols) Volume: 836 Pages: 99-115
  • DOI: 10.1007/978-1-61779-498-8_7
  • ISBN: 9781617794971, 9781617794988
  • Peer Reviewed
• [Journal Article] ISCSM2011 Chondroitin sulfate E-type structure at tumor cell surface is involved in experimental metastasis (2012)
  • Author(s): Sugahara, K., and Mizumoto, S.
  • Journal Title: Advances in Experimental Medicine and Biology Volume: 749 Pages: 33-45
  • DOI: 10.1007/978-1-4614-3381-1_3
  • ISBN: 9781461433804, 9781461433811
  • Peer Reviewed
• [Journal Article] Disorder of Biosynthesis of Dermatan Sulfate Causes a New Type of Ehlers-Danlos Syndrome (2011)
  • Author(s): Kazuyuki Sugahara and Shuji Mizumoto
  • Journal Title: Trends in Glycoscience and Glycotechnology Volume: 23 Issue: 132 Pages: 197-199
  • DOI: 10.4052/tigg.23.197
  • NAID: 10030388941
  • ISSN: 0915-7352, 1883-2113
  • Peer Reviewed
• [Journal Article] Involvement of HNK-1 sulfotransferase in the biosynthesis of chondro itin sulfate and the GlcA(3-O-sulfate)-Gal-Gal-Xyl tetrasaccharide found in α-thrombomodulin from human urine (2011)
  • Author(s): Taishi Hashiguchi
  • Journal Title: J.Biol.Chem Volume: 286 Issue: 38 Pages: 33003-33011
  • DOI: 10.1074/jbc.m111.279174
  • Peer Reviewed
• [Journal Article] Faulty initiation of proteoglycan synthesis causes cardiac and joint defects (2011)
  • Author(s): Baasanjav, S., Al-Gazali, L., Hashiguchi, T., Mizumoto, S., Fischer, B., Horn, D., Seelow, D., Ali, B.R., Aziz, S.A.A., Langer, R., Saleh,A.A.H., Becker, C., Nunberg,G., Cantagrel, V., Gleeson, J.G., Gomez, D., Michel, J-.B., Stricker, S., Lindner, T.H., Nunberg, P., Sugahara, K., Mundlos, S., Hoffmann, K.
  • Journal Title: American Journal of Human Genetics Volume: 89 Issue: 1 Pages: 15-27
  • DOI: 10.1016/j.ajhg.2011.05.021
  • Peer Reviewed
• [Presentation] サメヒレ軟骨コンドロイチン硫酸由来の新規な六糖配列の単離 (2012)
  • Author(s): 水本秀二,村越早織,Kittiwan Kalayanamitra, Sarama Sathyaseelan Deepa, 福井成行, Prachya Kongtawelert, 山田修平, 菅原一幸
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場およびマリンメッセ福岡、(ポスター発表)
  • Year and Date: 2012-12-15
• [Presentation] Receptor for Advanced Glycation End-products (RAGE) functions as areceptor for glycosaminoglycans involved in pulmonary metastasis (2012)
  • Author(s): Shuji MIZUMOTO, Jun TAKAHASHI,Kazuyuki SUGAHARA
  • Organizer: The 10th International Symposium for Future Drug Discovery and Medical Care
  • Place of Presentation: Hokkaido Univ.、(Poster& Short talk)
  • Year and Date: 2012-10-03
• [Presentation] RAGEは癌細胞の肺転移に関わるコンドロイ チン硫酸の受容体として機能する (2012)
  • Author(s): 水本秀二,高橋潤, 菅原一幸
  • Organizer: 第31回日本糖質学会年会
  • Place of Presentation: 鹿児島市民文化ホール、(口頭発表)and Kazuyuki Sugahara、
  • Year and Date: 2012-09-20
• [Presentation] Novel highly sulfated hexasaccharide sequences isolated from chondroitin sulfate of shark fin cartilage: Insights into the sugar sequences involved in brain development (2012)
  • Author(s): Shuji Mizumoto, Saori Murakoshi,Kittiwan Kalayanamitra, Sarama Sathyaseelan Deepa, Shigeyuki Fukui, Prachya Kongtawelert, Shuhei Yamada, and Kazuyuki Sugahara
  • Organizer: 2012年度包括型脳科学研究推進支援ネットワーク・夏のワークショップ
  • Place of Presentation: 仙台国際センター、(ポスター発表)
  • Year and Date: 2012-07-26
• [Presentation] Receptor for Advanced Glycation End Products (RAGE)は癌細胞の肺転移に関わる コンドロイチン硫酸の受容体として機能する (2012)
  • Author(s): 水本秀二,高橋潤,菅原一幸
  • Organizer: 日本薬学会北海道支部第138回例会
  • Place of Presentation: 札幌コンベンションセンター、(口頭発表)
  • Year and Date: 2012-06-16
• [Presentation] グルクロン酸転移酵素-Iの変異によって引き起こされる新規ラーセン様症候群 (2012)
  • Author(s): 水本秀二,Sevjidmaa Baasanjav,LihadhAl-Gazali,橋口太志,他19名
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学、(口頭発表)
  • Year and Date: 2012-03-29
• [Presentation] グルクロン酸転移酵素-Iの変異によって引き起こされる新規ラーセン様症候群 (2012)
  • Author(s): ◯水本秀二, Baasanjav S, Al-Gazali L, 橋口太志, Mundlos S, Hoffmann K, 菅原一幸 et al.
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学(札幌市)
• [Presentation] ○高橋潤, 水本秀二 , 菅原一幸 (2012)
  • Author(s): ○高橋潤, 水本秀二 , 菅原一幸
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学(札幌市)
• [Presentation] Loss-of-function mutation of glucuronyltransferase-I causes Larsen-like syndrome (2011)
  • Author(s): S. Baasanjav, L. Al-Gazali, T. Hashiguchi, S. Mizumoto, 他19名
  • Organizer: 7th International Conference on Proteoglycans
  • Place of Presentation: Q Station(Australia)、(Poster presentation)
  • Year and Date: 2011-10-18
• [Presentation] Loss-of-function mutations of dermatan 4-O-sulfotransferase-1 cause a new type of Ehlers-Danlos syndrome (2011)
  • Author(s): Shuji Mizumoto, Noriko Miyake, Tomoki Kosho, Shuhei Yamada, Kazuyuki Sugahara, and Naomichi Matsumoto
  • Organizer: The 9th International Symposium for Future Drug Discovery and Medical Care
  • Place of Presentation: Hokkaido Univ、(Poster)
  • Year and Date: 2011-09-30
• [Presentation] A deficiency of glycosaminoglycans causes cardiac and joint disorders (2011)
  • Author(s): Sevjidmaa Baasanjav, Lihadh Al-Gazali, Taishi Hashiguchi, Shuji Mizumoto , 他19名
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館、(口頭&ポスター発表)
  • Year and Date: 2011-09-24
• [Presentation] コンドロイチン硫酸/デルマタン硫酸の生合成に関わる酵素の欠損による骨・皮膚疾患 (2011)
  • Author(s): 水本秀二,三宅紀子,古庄知己, Mirjam H.H. van Roij, Beyhan Tuysuz,Stefan Mundlos, Stephen P. Robertson, 山田修平, 松本直通, 菅原一幸
  • Organizer: 第30回日本糖質学会年会
  • Place of Presentation: 長岡リリックホール、(口頭発表)
  • Year and Date: 2011-07-11
• [Presentation] コンドロイチン硫酸E構造の発現調節によるルイス肺癌細胞の転移抑制 (2011)
  • Author(s): 水本秀二、渡邊基夫、山田修平、菅原一幸
  • Organizer: 日本薬学会北海道支部第136例会
  • Place of Presentation: 札幌コンベンションセンター、(口頭発表)
  • Year and Date: 2011-05-21
• [Presentation] コンドロイチン硫酸/デルマタン硫酸の生合成に関わる酵素の欠損による骨・皮膚疾患 (2011)
  • Author(s): ○水本秀二, 三宅紀子, 古庄知己, Mirjam H.H. van Roij, Beyhan Tuysuz, Stefan Mundlos, Stephen P. Robertson, 山田修平, 松本直通, 菅原一幸
  • Organizer: 第30回日本糖質学会年会
  • Place of Presentation: 長岡リリックホール(新潟県)
• [Presentation] Loss-of-function mutations of dermatan 4-O-sulfotransferase-1 cause a new type of Ehlers-Danlos syndrome (2011)
  • Author(s): ◯Shuji Mizumoto, Noriko Miyake, Tomoki Kosho, Shuhei Yamada, Kazuyuki Sugahara, and Naomichi Matsumoto
  • Organizer: The 9th International Symposium for Future Drug Discovery and Medical Care
  • Place of Presentation: Hokkaido Univ. (Sapporo)
• [Presentation] A deficiency of glycosaminoglycans causes cardiac and joint disorders (2011)
  • Author(s): Baasanjav S, Al-Gazali L, Hashiguchi T, ○Mizumoto S, Sugahara K, Mundlos S, Hoffmann K. et al.
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都府)
• [Presentation] Loss-of-function mutation of glucuronyltransferase-I causes Larsen-like syndrome (2011)
  • Author(s): Baasanjav S, Al-Gazali L, Hashiguchi T, ○Mizumoto S, Sugahara K, Mundlos S, Hoffmann K. et al.
  • Organizer: 7th International Conference on Proteoglycans
  • Place of Presentation: Q Station (Australia)
• [Presentation] Receptor for Advanced Glycation End Products (RAGE)は癌細胞の肺転移に関わるコンドロイチン硫酸の受容体として機能する
  • Author(s): ○水本秀二, 高橋潤, 菅原一幸
  • Organizer: 日本薬学会北海道支部第138回例会
  • Place of Presentation: 札幌コンベンションセンター(札幌)
• [Presentation] Novel highly sulfated hexasaccharide sequences isolated from chondroitin sulfate of shark fin cartilage: Insights into the sugar sequences involved in brain development
  • Author(s): ○Shuji Mizumoto, Saori Murakoshi, Kittiwan Kalayanamitra, Sarama Sathyaseelan Deepa, Shigeyuki Fuku5, Prachya Kongtawelert, Shuhei Yamada, and Kazuyuki Sugahara
  • Organizer: 2012年度 包括型脳科学研究推進支援ネットワーク・夏のワークショップ
  • Place of Presentation: 仙台国際センター(仙台)
• [Presentation] RAGEは癌細胞の肺転移に関わるコンドロイチン硫酸の受容体として機能する
  • Author(s): ○水本秀二, 高橋潤, 菅原一幸
  • Organizer: 第31回日本糖質学会年会
  • Place of Presentation: 鹿児島市民文化ホール(鹿児島)
• [Presentation] Receptor for Advanced Glycation End-products (RAGE) functions as a receptor for glycosaminoglycans involved in pulmonary metastasis
  • Author(s): ◯Shuji MIZUMOTO, Jun TAKAHASHI, Kazuyuki SUGAHARA
  • Organizer: The 10th International Symposium for Future Drug Discovery and Medical Care
  • Place of Presentation: Hokkaido Univ.(Sapporo)
• [Presentation] サメヒレ軟骨コンドロイチン硫酸由来の新規な六糖配列の単離
  • Author(s): ◯水本秀二, 村越早織, Kittiwan Kalayanamitra, Sarama Sathyaseelan Deepa, 福井成行, Prachya Kongtawelert, 山田修平, 菅原一幸
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場(福岡)
• [Book] Walter De Gruyter, Berlin, Germany (2012)
  • Author(s): Shuji MIZUMOTO and Kazuyuki SUGAHARA、Bone and Skin Disorders Caused by a Disturbance in the Bioynthesis of Chondroitin Sulfate and Dermatan Sulfate
  • Publisher: Extracellular matrix: Pathobiology and signaling, (N. Karamanos ed.)
• [Book] Bone and Skin Disorders Caused by a Disturbance in the Bioynthesis of Chondroitin Sulfate and Dermatan Sulfate in Extracellular matrix: Pathobiology and signaling (2012)
  • Author(s): Shuji MIZUMOTO and Kazuyuki SUGAHARA
  • Publisher: Walter De Gruyter, Berlin, Germany
• [Remarks]
  • URL: http://www.lfsci.hokudai.ac.jp/labs/infmem/main.html
• [Remarks] 研究業績
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• [Remarks]
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• [Remarks]
  • URL: http://www.hokudai.ac.jp/news/120514_pr_lfsci.pdf
• [Remarks]
  • URL: http://www.cris.hokudai.ac.jp/cris/innovahome/press/press_20120516.html