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2013 Fiscal Year Final Research Report

Molecular Mechanism for Phosphate Sensing and Bone-Kidney Functional Interaction

Research Project

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Project/Area Number 23591227
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionResearch Institute, Osaka Medical Center for Maternal and Child Health

Principal Investigator

MICHIGAMI Toshimi  地方独立行政法人大阪府立病院機構大阪府立母子保健総合医療センター(研究所), 環境影響部門, 部長 (00301804)

Project Period (FY) 2011 – 2013
Keywordsリン代謝 / 骨細胞 / FGF23 / DMP1 / PHEX / ビタミンD
Research Abstract

Recent studies suggest the roles of osteocyte in phosphate metabolism, although the underlying mechanisms remain unclear. In the current study, the roles of osteocytes in phosphate metabolism were investigated using the osteoblasts and osteocytes isolated from mouse long bones. The expression of Fgf23, Dmp1, Phex and Fam20c was higher in osteocytes than osteoblasts. In the osteocytes isolated from Phex-deficient Hyp mice, the expressions of Dmp1, Fam20c and Pit1 as well as that of Fgf23 were up-regulated. 24-hour treatment with 1,25-dihydroxyvitamin D markedly increased the expression of Fgf23. On the other hand, 24-hour treatment with high phosphate did not alter the expression of Fgf23, although it markedly increased the expression of Dmp1. These results suggest that chronic phosphate load is required for the increase of FGF23 production.

  • Research Products

    (25 results)

All 2014 2013 2012 2011

All Journal Article (8 results) (of which Peer Reviewed: 7 results) Presentation (17 results)

  • [Journal Article] Dysregulated gene expression in the primary osteoblasts and osteocytes isolated from hypophosphatemic Hyp mice2014

    • Author(s)
      Miyagawa K, Yamazaki M, Kawai M, Nishino J, Koshimizu T, Ohata Y, Tachikawa K, Mikuni-Takagaki Y, Kogo M, Ozono K, Michigami T
    • Journal Title

      PLoS One

      Volume: 9 Pages: e93840

    • DOI

      10.1371/journal.pone.0093840

    • Peer Reviewed
  • [Journal Article] Elevated fibroblast growth factor 23 exerts its effects on placenta and regulates vitamin D metabolism in pregnancy of Hyp mice2014

    • Author(s)
      Ohata Y, Yamazaki M, Kawai M, Tsugawa N, Tachikawa K, Koinuma T, Miyagawa K, Kimoto A, Nakayama M, Namba N, Yamamoto H, Okano T, Ozono K, Michigami T
    • Journal Title

      J Bone Miner Res

      Volume: (E-pub)

    • DOI

      10.1002/jbmr.2186

    • Peer Reviewed
  • [Journal Article] Sympathetic activation induces skeletal Fgf23 expression in a circadian rhythm-dependent manner2014

    • Author(s)
      Kawai M, Kinoshita S, Shimba S, Ozono K, Michigami T
    • Journal Title

      J Biol Chem

      Volume: 289 Pages: 1457-1466

    • DOI

      10.1074/jbc.M113.500850

    • Peer Reviewed
  • [Journal Article] Extracellular phosphate as a signaling molecule2013

    • Author(s)
      Michigami T
    • Journal Title

      Contrib Nephrol

      Volume: 180 Pages: 14-24

    • DOI

      10.1159/000346776

  • [Journal Article] Regulatory mechanisms for the development of growth plate cartilage2013

    • Author(s)
      Michigami T
    • Journal Title

      Cell Mol Life Sci

      Volume: 70 Pages: 4213-4221

    • DOI

      10.1007/s00018-013-1346-9

    • Peer Reviewed
  • [Journal Article] Retention of fetuin-A in renal tubular lumen protects the kidney from nephrocalcinosis in rats2013

    • Author(s)
      Matsui I, Hamano T, Mikami S, Inoue K, Shimomura A, Nagasawa Y, Michigami T, Ohnishi T, Fujii N, Nakano C, Kusunoki Y, Kitamura H, Iwatani H, Takabatake Y, Kaimori JY, Matsuba G, Okoshi K, Kimura-Suda H, Tsubakihara Y, Rakugi H, Isaka Y
    • Journal Title

      Am J Physiol Renal Physiol

      Volume: 304 Pages: F751–760

    • DOI

      10.1152/ajprenal.00329.2012

    • Peer Reviewed
  • [Journal Article] FGF23 suppresses chondrocyte proliferation in the presence of soluble a-Klotho both in vitro and in vivo2013

    • Author(s)
      Kawai M, Kinoshita S, Kimoto A, Hasegawa Y, Miyagawa K, Yamazaki M, Ohata Y, Ozono K, Michigami T
    • Journal Title

      J Biol Chem

      Volume: 288 Pages: 2414-2427

    • DOI

      10.1074/jbc.M112.410043

    • Peer Reviewed
  • [Journal Article] Vinculin functions as a regulator of chondrogenesis2012

    • Author(s)
      Koshimizu T, Kawai M, Kondou H, Tachikawa K, Sakai N, Ozono K, Michigami T
    • Journal Title

      J Biol Chem

      Volume: 287 Pages: 15760-15775

    • DOI

      10.1074/jbc.M111.308072

    • Peer Reviewed
  • [Presentation] Fetal stage-specific mineral metabolism in Hyp mice is associated with effects of FGF23 on placenta2013

    • Author(s)
      Ohata Y, Yamazaki M, Kawai M, Tachikawa K, Koinuma T, Miyagawa K, Kimoto A, Nakayama M, Namba N, Yamamoto H, Ozono K, Michigami T
    • Organizer
      35th Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Bartimore
    • Year and Date
      20131004-07
  • [Presentation] Signaling of extracellular inorganic phosphate induces the expression of Dmp1 in osteoblast/osteocytes lineage cells via Na^+/Pi Co-transporter and MEK/ERK pathway2013

    • Author(s)
      Nishino J, Miyagawa K, Kawai M, Yamazaki M, Tachikawa K, Mikuni-Takagaki Y, Kogo M, Ozono K, Michigami T
    • Organizer
      35th Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Bartimore
    • Year and Date
      20131004-07
  • [Presentation] 2013. Sympathetic activation induces skeletal Fgf23 expression in a circadian rhythm dependent manner2013

    • Author(s)
      Kawai M, Kinoshita S, Shimba S, Ozono K, Michigami T
    • Organizer
      35th Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Bartimore
    • Year and Date
      20131004-07
  • [Presentation] Osteoclastic bone resorption might be involved in the secretion of FGF23 into circulation2012

    • Author(s)
      Yamazaki M, Miyagawa K, Ohata Y, Kawai M, Ozono K, Michigami T
    • Organizer
      34th Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Minneapolis
    • Year and Date
      20121012-15
  • [Presentation] FGF23 suppresses chondrocyte proliferation and maturation in the presence of soluble a-Klotho both in vitro and in vivo2012

    • Author(s)
      Kawai M, Kinoshita S, Ohata Y, Miyagawa K, Yamazaki M, Ozono K, Michigami T
    • Organizer
      34th Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Minneapolis
    • Year and Date
      20121012-15
  • [Presentation] FGF23は軟骨細胞増殖をリン代謝非依存性に抑制し,X連鎖性低リン性くる病に伴う低身長の一因となりうる2012

    • Author(s)
      川井正信,木下さおり,大幡泰久,大薗惠一,道上敏美
    • Organizer
      第46回日本小児内分泌学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      20120927-29
  • [Presentation] 骨細胞と骨外臓器との連関2012

    • Author(s)
      道上敏美
    • Organizer
      第30回日本骨代謝学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      20120719-21
  • [Presentation] 骨軟化症を合併する抗ミトコンドリア抗体(M2)陽性Fanconi症候群の近位尿細管ではNaPi-2cと共にメガリンの発現も低下する2012

    • Author(s)
      小林郁江,今西康雄,永田友貴,山形雅代,蔵城雅文,石村栄治,道上敏美
    • Organizer
      第30回日本骨代謝学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      20120719-21
  • [Presentation] FGF23の血中分泌過程における破骨細胞性骨吸収の関与の可能性2012

    • Author(s)
      山﨑美和,宮川和晃,大幡泰久,川井正信,大薗惠一,道上敏美
    • Organizer
      第30回日本骨代謝学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      20120719-21
  • [Presentation] FGF23は可溶型klotho存在下で軟骨細胞の増殖・成熟を抑制する2012

    • Author(s)
      川井正信,木下さおり,大幡泰久,宮川和晃,山﨑美和,大薗惠一,道上敏美
    • Organizer
      第30回日本骨代謝学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      20120719-21
  • [Presentation] 胎児特異的リン代謝:リン経胎盤輸送からみた新知見2011

    • Author(s)
      大幡泰久,道上敏美,大薗惠一
    • Organizer
      第56回日本未熟児新生児学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      20111113-15
  • [Presentation] XLHモデルHypマウスにおける胎児血中リン値維持機構の存在-FGF23および胎盤の関与2011

    • Author(s)
      大幡泰久,宮川和晃,山﨑美和,岡田知子,川井正信,平井治彦,大薗惠一,道上敏美
    • Organizer
      第45回日本小児内分泌学会学術集会
    • Place of Presentation
      埼玉
    • Year and Date
      20111006-08
  • [Presentation] 1,25(OH)_2D and PTH up-regulate Rankl while down-regulate Phex and dmp1 in primary osteocytes isolated from mouse bones2011

    • Author(s)
      Miyagawa K, Ozono K, Tachikawa K, Kawai M, Mikuni-Takagaki Y, Kogo M, Michigami T
    • Organizer
      33^<th> Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      San Diego
    • Year and Date
      20110916-20
  • [Presentation] Analysis of the roles of FGF23 in fetus-specific mineral metabolism using Hyp mice2011

    • Author(s)
      Ohata Y, Miyagawa K,Yamazaki M, Okada T, Kawai M, Ozono K, Michigami T
    • Organizer
      IOF Regionals 2^<nd> Asis-Pacific Osteoporosis and Bone Meeting
    • Place of Presentation
      Gold Coast
    • Year and Date
      20110904-08
  • [Presentation] リン代謝調節細胞としての骨細胞の役割2011

    • Author(s)
      道上敏美
    • Organizer
      第29回日本骨代謝学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      20110728-30
  • [Presentation] 胎児期特異的ミネラル代謝調節機構におけるFGF23の関与─Hypマウスを用いた解析2011

    • Author(s)
      大幡泰久,三浦弘司,山﨑美和,岡田知子,川井正信,大薗惠一,道上敏美
    • Organizer
      第29回日本骨代謝学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      20110728-30
  • [Presentation] Hypマウスの骨においては胎児期より既にFgf23及びDmp1の発現が増加している2011

    • Author(s)
      宮川和晃,大薗惠一,大幡泰久,川井正信,立川加奈子,高垣裕子,古郷幹彦,道上敏美
    • Organizer
      第29回日本骨代謝学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      20110728-30

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Published: 2015-07-16  

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