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Molecular identification and functional analysis of Na^+/Ca^<2+> exchanger (NCX) associated with osteoclastic bone resorption

Research Project

Project/Area Number 18592054
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionFukuoka Dental College

Principal Investigator

OKABE Koji  Fukuoka Dental College, DENTISTRY, Professor (80224046)

Co-Investigator(Kenkyū-buntansha) KAJIYA Hiroshi  Fukuoka Dental College, DENTISTRY, Assistant professor (80177378)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,790,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsosteoclast / bone resorption / Na^+ / Ca^<2+> exchanger / NCX / Ca^<2+> transport / NCX inhibitor / Knockout mice / Ca^<2+> influx mode / Na+ / NCX電流 / 細胞内Ca^<2+>濃度測定
Research Abstract

The plasma membrane Na^+/Ca^<2+> exchanger (NCX) is a bi-directional transporter that mediates the exchange of Na^+ for Ca^<2+> depending on the electrochemical gradients. Mammalian NCXs form a multigene family comprising NCX1, NCX2 and NCX3 isoforms. Although it has been known that NCX1 in rat osteoclasts is coupled with the Na^+/H^+ exchanger for regulation of intracellular Ca^<2+> concentration ([Ca^<2+>]_i), it is unclear what kind of NCX1 variants are expressed and whether the other two NCX isoforms are also present in mouse osteoclasts. To clarify the role of NCXs during bone resorption, we investigated the expression of NCXs, the ion transport via NCXs and the effects of NCX inhibitors on bone-resorbing activity in mouse osteoclasts. Using RT-PCR, immunocytochemical and Western blot methods, we detected three splice variants of NCX1 and NCX3, namely NCX1.3, NCX1.41 and NCX3.2. Of these, NCX1.41 is a newly identified splice variant. Low extracellular sodium ([Na^+]_o) solution increases the intracellular Ca^<2+> concentration via NCX transporter in fura-2 loaded osteoclasts. The [Na^+]_o-free solution induced [Ca^<2+>]_i increase was suppressed by benzyloxyphenyl NCX inhibitors. Bidirectional NCX-currents in mouse osteoclasts were recorded using the patch clamp method and could be suppressed with NCX inhibitors. NCX inhibitors also decreased the resorption pit area surrounding osteoclasts in a dose dependent manner. Furthermore, siRNAs targeted against NCX1.3, 1.41 and NCX3.2 expressed in mouse osteoclasts suppressed osteoclastic pit formation. These results show that three NCX variants are expressed in mouse osteoclasts and play an important role for Ca^<2+> transport and regulation during osteoclastic bone resorption.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (17 results)

All 2007 2006 1998

All Journal Article (5 results) (of which Peer Reviewed: 2 results) Presentation (12 results)

  • [Journal Article] Three Na^+/Ca^<2+> exchanger(NCX)variants are expressed in mouse osteoclasts and mediate calcium transport during bone resorptio.2007

    • Author(s)
      Jing-Ping Li, Kajiya H, Okamoto F, Nakao A, Iwamoto T, Okabe K.
    • Journal Title

      Endocrinology 148

      Pages: 2116-2125

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Three Na^+/Ca^<2+> exchanger(NCX)variants are expressed in mouse osteoclasts and mediate calcium transport during bone resorptio2007

    • Author(s)
      Jing-Ping Li, Kajiya H, Okamoto F, Nakao A, Iwamoto T, Okabe K
    • Journal Title

      Endocrinology 148

      Pages: 2116-2125

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Three Na^+/Ca^<2+> exchanger(NCX)variants are expressed in mouse osteoclasts and mediate calcium transport during bone resorptio2007

    • Author(s)
      Jing-Ping Li, Kajiya H, Okamoto F, Nakao A, Iwamoto T, Okabe K.
    • Journal Title

      Endocrinolog 148

      Pages: 2116-2125

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of three Na^+/Ca^<2+> exchanger(NCX)variants in mouse osteoclasts and their function role during bone resorption.2006

    • Author(s)
      Okabe K, Li JP, Kajiya H, Okamoto F, Nakao A, Fukushima H, Iwamoto T.
    • Journal Title

      J Bone Miner Res 24(suppl)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Expression of three Na^+/Ca^<2+> exchanger(NCX)variants in mouse osteoclasts and their function role during bone resorption2006

    • Author(s)
      Okabe K, Li JP, Kajiya H, Okamoto F, Nakao A, Fukushima H, Iwamoto T
    • Journal Title

      J Bone Miner Res 24(suppl)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 破骨細胞に出現するCl^-チャネル(ClC7)と骨吸収機能調節2007

    • Author(s)
      岡部幸司、鍛治屋浩、岡本富士雄
    • Organizer
      第49回歯科基礎医学会総会 サテライトシンポジウム
    • Place of Presentation
      札幌
    • Year and Date
      2007-08-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Cl-channel(ClC7)expressed in osteoclasts and the regulation of bone resorption2007

    • Author(s)
      Okabe K, Kajiya H, Okamoto F
    • Organizer
      The 49th Annual Meeting for Oral Biology(Satellite symposium)
    • Place of Presentation
      Sapporo
    • Year and Date
      2007-08-29
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] RANKL刺激により破骨細胞前駆細胞から自己分泌されるTNFαは、c-fos及びNFATclを介して破骨細胞形成を促進する2007

    • Author(s)
      中尾彰宏、福島秀文、岡本富士雄、鍛治屋浩、岡部幸司
    • Organizer
      第25回日本骨代謝学会
    • Place of Presentation
      大阪
    • Year and Date
      2007-07-20
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] RANKL-induced TNFa self-secretion from osteoclast-precusor cells promotes osteoclastgenesis via c-fos and NFATc12007

    • Author(s)
      Nakao A, Fukushima H, Okamoto F, Kajiya H, Okabe K
    • Organizer
      The 25th Annual Meeting for the Japanese Society for Bone and Mineral Research
    • Place of Presentation
      Osaka
    • Year and Date
      2007-07-20
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 常染色体優性大理石骨病typeIIはCLCN7点変異によるC1^-分泌抑制が一因である2007

    • Author(s)
      岡部幸司、鍛治屋浩、岡本富士雄、福島秀文
    • Organizer
      特定領域研究「生体膜トランスポートソームの分子構築と生理機能」ワークショップ、招待講演
    • Place of Presentation
      富士市
    • Year and Date
      2007-01-29
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 破骨細胞に発現する3種の Na^+/Ca^<2+>交換輸送体(NCX)とこれらの骨吸収における役割2007

    • Author(s)
      鍛治屋浩、岡本富士雄、中尾彰宏、岩本隆宏、岡部幸司
    • Organizer
      特定領域研究「生体膜トランスポートソームの分子構築と生理機能」ワークショップ、招待講演
    • Place of Presentation
      富士市
    • Year and Date
      2007-01-27
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Three types of Na^+/Ca^<2+> exchanger(NCX)expressed in osteoclasts and the role in bone resorption2007

    • Author(s)
      Kajiya H, Okamoto F, Nakao A, Iwamoto T, Okabe K
    • Organizer
      Workshop on "Molecular construction and physiology function of transportsorm in biomembrane"
    • Place of Presentation
      Fuji city
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Decrease in Cl-secretion with CLCN7 point mutation in osteoclasts induces the autosomal dominant osteopetrosis typeII2007

    • Author(s)
      Okabe K, Kajiya H, Okamoto F, Fukushima H
    • Organizer
      Workshop on "Molecular construction and physiology function of transportsorm in biomembrane"
    • Place of Presentation
      Fuji city
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 破骨細胞に発現する3種のNa^+/Ca^<2+>交換輪送体(NCX)とこれらの骨吸収への関与2006

    • Author(s)
      鍛治屋浩、岡本富士雄、中尾彰宏、福島秀文、岡部幸司
    • Organizer
      第24回日本骨代謝学会
    • Place of Presentation
      東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Expression of three Na^+/Ca^<2+> exchanger(NCX)variants in mouse osteoclasts and their function role during bone resorption.2006

    • Author(s)
      Okabe K, Li JP, Kajiya H, Okamoto F, Nakao A, Fukushima H, Iwamoto T.
    • Organizer
      28th Annual Meeting of the American Society ofr Bone and Mineral Research
    • Place of Presentation
      Philadelphia, USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Expression of three Na^+/Ca^<2+> exchanger(NCX)variants in mouse osteoclasts and their function role during bone resorption2006

    • Author(s)
      Okabe K, Li JP, Kajiya H, Okamoto F, Nakao A, Fukushima H, Iwamoto T.
    • Organizer
      The 28th Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Philadelphia
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Three types of Na^+/Ca^<2+> exchanger(NCX)expressed in osteoclasts and these involvement in bone resorption1998

    • Author(s)
      Kajiya H, Okamoto F, Nakao A, Fukushima H, Okabe K
    • Organizer
      The 24th Annual Meeting for the Japanese Society for Bone and Mineral Research
    • Place of Presentation
      Tokyo
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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