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The functional analysis of the nucleotide-sugar transporter SLC35D1 and SLC35D2 in cartilage using knockout mice model.

Research Project

Project/Area Number 21390428
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionKobe Pharmaceutical University (2012-2013)
National Research Institute for Child Health and Development (2009-2011)

Principal Investigator

HIRAOKA SHUICHI  神戸薬科大学, 薬学部, 研究生 (20291156)

Co-Investigator(Renkei-kenkyūsha) ASAHARA Hiroshi  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (70294460)
Project Period (FY) 2009-04-01 – 2013-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2012: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2011: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Keywords糖ヌクレオチド輸送体 / 軟骨疾患 / コンドロイチン硫酸 / 骨軟骨異形成症 / 関節軟骨 / 糖鎖 / 生体分子 / 関節疾患
Research Abstract

The chondroitin sulfate (CS) is required for various cartilage functions. The nucleotide-sugar transporter SLC35D1 and SLC35D2 supply substrates to polymerize CS. I analyzed compound mutant mice harboring in SLC35D1 KO and hypomorphic, and SLC35D2 KO mutations. As a result of investigations, I clarified that both transporters play the essential role for CS synthesis of proteoglycans in cartilage, (2) various combinations of mutant alleles of both coding genes induce to step wise reduction of CS producing level in cartilage, (3) the skeletal abnormalities are observed in response to the reduction level of CS synthesis. I also investigated SLC35D1 function using Flox mutant of SLC35d1 mice. I observed critical loss of intestinal functions in adult mice lacking SLC35D1 by inducible gene disruption strategy. The nobel function of SLC35D1 in intestine is useful to survey unidentified leaky-type mutations of SLC35D1 in human, which may survive during perinatal period.

Report

(5 results)
  • 2013 Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (20 results)

All 2013 2012 2011 2010 2009

All Journal Article (6 results) (of which Peer Reviewed: 3 results) Presentation (14 results)

  • [Journal Article] CCN3 protein participates in bone regeneration as an inhibitory factor2013

    • Author(s)
      Matsushita Y, Sakamoto K, Tamamura Y, Shibata Y, Minamizato T, Kihara T, Ito M, Katsube K, Hiraoka S
    • Journal Title

      J Biol chem

      Volume: 288 Pages: 19973-19985

    • Related Report
      2013 Final Research Report
  • [Journal Article] CCN3 protein participates in bone regeneration as an inhibitory factor.2013

    • Author(s)
      Matsushita Y, Sakamoto K, Tamamura Y, Shibata Y, Minamizato T, Kihara T, Ito M, Katsube K, Hiraoka S, Koseki H, Harada K, Yamaguchi A.
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 288 Issue: 27 Pages: 19973-19985

    • DOI

      10.1074/jbc.m113.454652

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CCN3 inhibits neointimal hyperplasia through modulation of smooth muscle cell growth and migration2010

    • Author(s)
      Shimoyama T,Hiraoka S, et al
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 30 Issue: 4 Pages: 675-682

    • DOI

      10.1161/atvbaha.110.203356

    • Related Report
      2013 Final Research Report
  • [Journal Article] CCN3 inhibits neointimal hyperplasia through modulation of smooth muscle cell growth and migration2010

    • Author(s)
      Shimoyama T, Hiraoka S, et al.
    • Journal Title

      Arteriosclerosis, Thrombosis, and Vascular Biology

      Volume: 30 Pages: 675-682

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of loss-of-function mutations of SLc35Dl in patients with Schneckenbecken dysplasia, but not with other severe spondylodysplastic dysplasias group diseases2009

    • Author(s)
      Furuichi T, Kayserili H, Hiraoka S, et al
    • Journal Title

      J Med Genet

      Volume: 46 Issue: 8 Pages: 562-868

    • DOI

      10.1136/jmg.2008.065201

    • Related Report
      2013 Final Research Report
  • [Journal Article] Identification of loss-of function mutations of SLC35D1 in patients with Schneckenbecken dysplasia, but not with other severe spondylodysplastic dysplasias group diseases2009

    • Author(s)
      Furuichi T, et al.
    • Journal Title

      Journal of medical genetics 46(8)

      Pages: 562-568

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 組哉特異的遺伝子破壊マウスを利用した糖ヌクレオチド輸送体SLc35DlおよびSLc35D2の軟骨分化・機能維持における機能解析2012

    • Author(s)
      平岡秀一、他4名
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      マリンメッセ福岡
    • Year and Date
      2012-12-11
    • Related Report
      2013 Final Research Report
  • [Presentation] ヌクレオチド輸送体SLc35DlおよびSLc35D2を媒介したグリコサミノグリカン合成は初期匪の正常な分化に必要である2011

    • Author(s)
      平岡秀一、他4名
    • Organizer
      第33回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2011-12-09
    • Related Report
      2013 Final Research Report
  • [Presentation] ヌクレオチド輸送体SLC35D1およびSLG35D2を媒介したグリコサミノグリカン合成は初期胚の正常な分化に必要である2011

    • Author(s)
      平岡秀一、北川裕之、柳下正樹、古関明彦、浅原弘嗣
    • Organizer
      第33回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2011-12-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] 糖ヌクレオチド輸送体による器官形成制御の分子メカニズム2011

    • Author(s)
      平岡秀一
    • Organizer
      埼玉大学分子生物学科講演会
    • Place of Presentation
      埼玉大学
    • Year and Date
      2011-11-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] 糖ヌクレオチド輸送体2011

    • Author(s)
      平岡秀一
    • Organizer
      第26回日本整形外科学会基礎学術集会
    • Place of Presentation
      群馬県民会館
    • Year and Date
      2011-10-20
    • Related Report
      2013 Final Research Report 2011 Annual Research Report
  • [Presentation] A practical approach to identify the roles of glycosylations in organ development using Nucleotide-Sugar transporter knockout mice2011

    • Author(s)
      平岡秀一
    • Organizer
      第28回内藤カンファレンス
    • Place of Presentation
      湘南国際村
    • Year and Date
      2011-07-29
    • Related Report
      2013 Final Research Report
  • [Presentation] A practical approach to identify the roles of glycosylations in organ development using Nucleotide-Sugar transporter knockout mice2011

    • Author(s)
      平岡秀一
    • Organizer
      第28回内藤コンファレンス
    • Place of Presentation
      湘南国際村
    • Year and Date
      2011-07-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] 組哉特異的遺伝子破壊マウスを利用した糖ヌクレオチド輸送体SLc35DlおよびSLc35D2の軟骨分化・機能維持における機能解析2011

    • Author(s)
      平岡秀一, 他3名
    • Organizer
      第24回日本軟骨代謝学会学術集会
    • Place of Presentation
      九州大学医学部
    • Year and Date
      2011-03-04
    • Related Report
      2013 Final Research Report
  • [Presentation] 組織特異的遺伝子破壊マウスを利用した糖ヌクレオチド輸送体SLC35D1およびSLC35D2の軟骨分化・機能維持における機能解析2011

    • Author(s)
      平岡秀一、中村英一郎、古関明彦、浅原弘嗣
    • Organizer
      第24回日本軟骨代謝学会学術集会
    • Place of Presentation
      九州大学医学部
    • Year and Date
      2011-03-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] 糖ヌクレオチド輸送体による器官形成制御の分子メカニズム2010

    • Author(s)
      平岡秀一
    • Organizer
      第11回日本運動器科学研究会
    • Place of Presentation
      軽井沢万平ホテル
    • Year and Date
      2010-09-09
    • Related Report
      2013 Final Research Report 2010 Annual Research Report
  • [Presentation] 糖ヌクレオチド輸送体SLc35D2の軟骨コンドロイチン硫酸合成に対する寄与2010

    • Author(s)
      平岡秀一、他4名
    • Organizer
      第23回日本軟骨代謝学会学術集会
    • Place of Presentation
      鹿児島県医師会館
    • Year and Date
      2010-04-03
    • Related Report
      2013 Final Research Report
  • [Presentation] 糖ヌクレオチド輸送体SLC35D2の軟骨コンドロイチン硫酸合成に対する寄与2010

    • Author(s)
      平岡秀一、泉奈都子、柳下正樹、浅原弘嗣
    • Organizer
      第23回日本軟骨代謝学会学術集会
    • Place of Presentation
      鹿児島県医師会館
    • Year and Date
      2010-04-03
    • Related Report
      2010 Annual Research Report
  • [Presentation] ヌクレオチド輸送体ScL35D2は軟骨プロテオグリカンのコンドロイチン硫酸合成に寄与する2009

    • Author(s)
      平岡秀一, 他3名
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2009-12-12
    • Related Report
      2013 Final Research Report
  • [Presentation] 糖ヌクレオチド輸送体SCL35D2は軟骨プロテオグリカンのコンドロイチン硫酸合成に寄与する2009

    • Author(s)
      平岡秀一, 他
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2009-12-12
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2019-12-17  

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