Functional analysis of glycosphingolipids in osteochondral homeostasis using knockout mice

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659661
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: Hokkaido University
• Principal Investigator: IWASAKI Norimasa 北海道大学, 医学(系)研究科(研究院), 教授 (30322803)
• Co-Investigator(Kenkyū-buntansha): TAKAHATA Masahiko 北海道大学, 北海道大学病院, 講師 (40374368) ; ONODERA Tomohiro 北海道大学, 大学院医学研究科, 助教 (70547174)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 骨・軟骨代謝学 / スフィンゴ糖脂質 / ガングリオシド / 遺伝子改変マウス

Research Abstract

Glycosphingolipids (GSLs) are ubiquitous membrane components that modulate transmembrane signaling and mediate cell-to-cell and cell-to-matrix interactions. The purpose of this study was to clarify the functional roles of GSLs in maintaining osteochondral homeostasis using different strains of GSLs synthase knockout (KO) mice. Although all strains of KO mice developed and grew normally, osteoarthritic changes were dramatically enhanced with aging. IL-1 stimulation of chondrocytes from KO mice significantly increased MMP-13 mRNA expression and apoptosis. In addition, KO mice delayed enchondral ossification during fracture repair process. These findings indicate that GSLs have a chondro-/osteo- protective role and prevent disease progression, although GSLs are not essential for osteochondral tissue development in young mice.

Research Products

• [Journal Article] Depletion of gangliosides enhances cartilage degradation in mice (2014)
  • Author(s): Sasazawa F, Onodera T, Yamashita T, Seito N, Tsukuda Y, Fujitani N, Shinohara Y, Iwasaki N
  • Journal Title: Osteoarthritis Cartilage Volume: 22 Pages: 313-322
  • DOI: 10.1016/j.joca.2013.11.015
  • Peer Reviewed
• [Journal Article] Ganglioside GM3 has an essential role in the pathogenesis and progression of rheumatoid arthritis (2012)
  • Author(s): Tsukuda Y, Iwasaki N, Seito N, Kanayama M, Fujitani N, Shinohara Y, Kasahara K, Onodera T, Suzuki K, Asano T, Minami A, Yamashita T
  • Journal Title: PLoS One Volume: 7 Pages: e40136
  • DOI: 10.1371/journal.pone.0040136
  • Peer Reviewed
• [Journal Article] Interruption of glycosphingolipid synthesis enhances osteoarthritis development in mice (2012)
  • Author(s): Seito N, Yamashita T, Tsukuda Y, Matsui Y, Urita A, Onodera T, Mizutani T, Haga H, Fujitani N, Shinohara Y, Minami A, Iwasaki N
  • Journal Title: Arthritis Rheum Volume: 64 Pages: 2579-2588
  • DOI: 10.1002/art.34463
  • Peer Reviewed
• [Presentation] Depletion of Gangliosides Enhances Cartilage Degradation through the Upregulation of Chondrocyte Apoptosis and Matrix Degrading Enzyme Expression (2014)
  • Author(s): Sasazawa F, Onodera T, Yamashita T, Fujitani N, Shinohara Y, Iwasaki N
  • Organizer: 60th ORS annual meeting
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 20140315-18
• [Presentation] Lack of GD3 Synthase Enhances Cartilage Degradation in Murine Osteoarthritis Models in Vitro (2014)
  • Author(s): Momma D, Onodera T, Matsuoka M, Sasazawa F, Iwasaki N
  • Organizer: 60th ORS annual meeting
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 20140315-18
• [Presentation] スフィンゴ糖脂質の欠損は変形性関節症の進行を助長する (2014)
  • Author(s): 清藤直樹、山下匡、佃幸憲、松井雄一郎、瓜田淳、小野寺智洋、藤谷直樹、篠原康郎、三浪明男、岩崎倫政
  • Organizer: 第27回日本軟骨代謝学会
  • Place of Presentation: 京都
  • Year and Date: 20140228-0301
• [Presentation] ガングリオシド欠損はマトリックス分解酵素発現の亢進を介してOA進行を助長する (2014)
  • Author(s): 笹沢史生、小野寺智洋、山下匡、藤谷直樹、篠原康郎、岩崎倫政
  • Organizer: 第27回日本軟骨代謝学会
  • Place of Presentation: 京都
  • Year and Date: 20140228-0301
• [Presentation] GD3合成酵素の欠損は変形性関節症を助長する (2014)
  • Author(s): 門間太輔、小野寺智洋、笹沢史生、松岡正剛、岩崎倫政
  • Organizer: 第126回北海道整形災害外科学会
  • Place of Presentation: 札幌
  • Year and Date: 20140201-02
• [Presentation] ガングリオシド欠損は軟骨細胞アポトーシスや基質分解酵素発現亢進を介して変形性関節症を進行させる (2013)
  • Author(s): 笹沢史生、小野寺智洋、山下匡、岩崎倫政
  • Organizer: 第28回日本整形外科学会基礎学術集会
  • Place of Presentation: 千葉
  • Year and Date: 20131017-18
• [Presentation] Delection of Gangliosides Enhances Cartilage Degradation in Murine of Osteoarthritis (2013)
  • Author(s): Sasazawa F, Onodera T, Yamashita T, Fujitani N, Shinohara Y, Iwasaki N
  • Organizer: 2013 ORS Annual Meeting
  • Place of Presentation: Henry B. Gonzalez Convention Center , San Antonio, TX, USA
  • Year and Date: 20130126-29
• [Presentation] ガングリオシドGM3は関節リウマチの発症、進行において重要な役割を担う (2012)
  • Author(s): 佃幸憲、岩崎倫政、清藤直樹、金山剛士、藤谷直樹、篠原康郎、笠原靖彦、小野寺智洋、浅野毅、三浪明男、山下匡
  • Organizer: 第27回日本整形外科学会基礎学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 20121026-27
• [Presentation] スフィンゴ糖脂質の欠損は変形性関節症の進行を助長する (2012)
  • Author(s): 清藤直樹、山下匡、佃幸憲、松井雄一郎、瓜田淳、小野寺智洋、藤谷直樹、篠原康郎、三浪明男、岩崎倫政
  • Organizer: 第27回日本整形外科学会基礎学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 20121026-27
• [Presentation] 軟骨細胞におけるガングリオシドの欠損はマウス変形性関節症の進行を助長する (2012)
  • Author(s): 笹沢史生、岩崎倫政、山下匡、清藤直樹、小野寺智洋、佃幸憲、三浪明男
  • Organizer: 第27回日本整形外科学会基礎学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 20121026-27
• [Presentation] Interuption of glycosphingolipid and ganglioside synthesis enhances osteoarthritis development in mice (2012)
  • Author(s): Sasazawa F, Iwasaki N, Yamashita T, Seito N, Onodera T, Minami A
  • Organizer: Gordon Research Conferences
  • Place of Presentation: Ciocco Resort, Italy
  • Year and Date: 20120422-27
• [Presentation] Ganglioside GM3 has an essential role in the pathogenesis and progression of rheumatoid arthritis (2012)
  • Author(s): Tsukuda Y, Iwasaki N, Seito N, Kanayama M, Fujitani N, Shinohara Y, Kasahara Y, Minami A, Yamashita T
  • Organizer: Gordon Research Conferences
  • Place of Presentation: Ciocco Resort, Italy
  • Year and Date: 20120422-27