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Regulatory Mechanism of RANK Gene Expression during Osteoclastic Differentiation of Bone Marrow Macrophage/Monocyte Lineage

Research Project

Project/Area Number 21590419
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionKobe University

Principal Investigator

KITAZAWA Riko  神戸大学, 大学院・医学研究科, 特命准教授 (00273780)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords破骨細胞 / RANK / 遺伝子プロモータ / 転写因子 / RANKL / 造血細胞
Research Abstract

Receptor activator of NF-kappaB(RANK) expressed on osteoclasts and their precursors is a receptor for RANK Ligand(RANKL). RANKL-RANK interaction induces genes essential for the differentiation of osteoclasts through the binding of NFATc1 to target gene promoters. We have cloned a 6-kb fragment containing the 5'-flanking region of the mouse RANK gene and have analyzed the binding elements such as PU. 1(-480), and MITF(-100). Here, we showed the regulatory mechanism of RANK gene transcription through the NFAT(-370) and CRE/AP-1 binding sites(-240). Furthermore, we have identified a novel alternative splicing variant of mouse RANK gene that contains a new intervening exon between exon 1 and exon 2 of mouse full-length RANK mRNA, and shown that variant RANK is a novel osteoclast suppressor that reduces the number of RANKL-induced mature osteoclasts mainly by negating the anti-apoptotic effect of RANKL.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (40 results)

All 2012 2011 2010 2009 Other

All Journal Article (24 results) (of which Peer Reviewed: 24 results) Presentation (11 results) Book (4 results) Remarks (1 results)

  • [Journal Article] A. p D116G mutation in CREB1 leads to novel multiple malformation syndrome resembling CrebA knockout mouse2012

    • Author(s)
      Kitazawa S, Kondo T, Mori K, Yokoyama N, Matsuo M, Kitazawa R.
    • Journal Title

      Human Mutation

      Volume: (in press)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] CIZ/NMP4 is expressed in B16 melanoma and forms a positive feedback loop with RANKL to promote migration of the melanoma cells2012

    • Author(s)
      Sakuma T, Nakamoto T, Hemmi H, Kitazawa S, Kitazawa R, Notomi T, Hayata, T, Ezura Y, Amagasa T, Noda M
    • Journal Title

      J Cell Physiol

      Volume: (in press)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pyruvate dehydrogenase kinase 4 induces bone loss at unloading by promoting Osteoclastogenesis2012

    • Author(s)
      Wang Y, Liul W, Masuyama R, Fukuyama R, Ito M, Zhang Q, Komori H, Murakami T, Moriishi T, Miyazaki T, Kitazawa R, Yoshida CA, Kawai Y, Izumi S, Komori T
    • Journal Title

      Bone

      Volume: 50 Pages: 409-419

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification and analysis of function of a novel splicing variant of mouse receptor activator of NF-kappaB2011

    • Author(s)
      Mukai S, Kitazawa R, Ishii J, Kondo T, Hakozaki A, Hosiuchi K, Kiyoshi M, Kitazawa S.
    • Journal Title

      Mol Cell Biochem

      Volume: 350 Pages: 29-38

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic Alteration by DNA Promoter Hypermethylation of Genes Related to Transforming Growth Factor-β(TGF-β) Signaling in Cancer(review). Sann Sanda Khin2011

    • Author(s)
      Kitazawa R, Kondo T, Idei Y, Fujimoto M, Haraguchi R, Mori K, Kitazawa S
    • Journal Title

      Cancers

      Volume: 3 Pages: 982-993

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Parathyroid hormone-responsive Smad3-related factor, Tmem119, promotes osteoblast differentiation and interacts with the bone morphogenetic protein-Runx2 pathway2011

    • Author(s)
      Hisa I, Inoue Y, Hendy GN, Canaff L, Kitazawa R, Kitazawa S, Komori T, Sugimoto T, Seino S, Kaji H
    • Journal Title

      J Biol Chem

      Volume: 286 Pages: 9787-9796

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chemerin regulates β-cell function in mice.2011

    • Author(s)
      Takahashi M, Okimura Y, Iguchi G, Nishizawa H, Yamamoto M, Suda K, Kitazawa R, Fujimoto W, Takahashi K, Zolotaryov FN, Hong KS, Kiyonari H, Abe T, Kaji H, Kitazawa S, Kasuga M, Chihara K, Takahashi Y.
    • Journal Title

      Scientific Reports

      Volume: 1 Issue: 1 Pages: 123-123

    • DOI

      10.1038/srep00123

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Carvedilol ameliorates low-turnover bone disease in nonobese type 2 diabetes2011

    • Author(s)
      Goto S, Fujii H, Kono K, NakaiK, Hamada H, Yamato H, Shinohara M, Kitazawa R, Kitazawa S, Nishi S, Fukagawa M
    • Journal Title

      Am J Nephrol

      Volume: 34 Pages: 281-290

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Carvedilol ameliorates low-turnover bone disease in non-obese type 2 diabetes2011

    • Author(s)
      Shunsuke Goto, Hideki Fujii, Keiji Kono, Kentaro Nakai, Yasuhiro Hamada, Hideyuki Yamato, Masami Shinohara, Riko Kitazawa, Sohei Kitazawa, Shinichi Nishi, and Masafumi Fukagaw
    • Journal Title

      Am J Nephrol

      Volume: 34(3) Issue: 3 Pages: 281-290

    • DOI

      10.1159/000330853

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pyruvate dehydrogenase kinase 4 induce bone loss at unloading by promoting Osteoclastogenesis2011

    • Author(s)
      Wang Y, Liul W, et al
    • Journal Title

      Bone

      Volume: 50 Pages: 409-419

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification and analysis of function of a novel splicing variant of mouse receptor activator of□NF-kappaB2011

    • Author(s)
      S.Mukai, et al.
    • Journal Title

      Molecular and Cellular Biochemistry

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic alteration by DNA promoter hypermethylation of genes related to transforming growth factor-β (TGF-β) signaling.2011

    • Author(s)
      Sann Sanda Khin, et al.
    • Journal Title

      Cancers

      Volume: 3 Pages: 982-993

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Depressed expression of Klotho and FGFR1 in hyperplastic parathyroid glands from uremic patients2010

    • Author(s)
      Komaba H, Goto S, Fujii H, Hamada Y, Kobayashi A, Shibuya K, Tominaga Y, Otsuki N, Nibu K, Kitazawa R, Fukagawa M
    • Journal Title

      Kidney Int

      Volume: 77 Pages: 232-238

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Oxidative and nitrosative stress and progression of diabetic nephropathy in type 2 diabetes2010

    • Author(s)
      Fujii H, Kono K, Nakai K, Goto S, Komaba H, Hamada Y, Shinohara M, Kitazawa R, Kitazawa S, Fukagawa M
    • Journal Title

      Am J Nephrol

      Volume: 31 Pages: 342-352

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of ultraviolet B-induced skintumor development in phospholipase Cknockout mice is associated with decreased apoptosis2010

    • Author(s)
      Oka M, Edamatsu H, Kunisada M, Dien S, Kitazawa R, Kataoka T, Nishigori C
    • Journal Title

      Carcinogenesis

      Volume: 31 Pages: 1897-1902

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The effect of the receptor for advanced glycation end products(RAGE) on bone metabolism under physiological and diabetic conditions2010

    • Author(s)
      Hamada Y, Kitazawa S, Kitazawa R, Kone K, Goto S, Komaba H, Fujii H, Yamamoto Y, Yamamoto H, Usami M, Fukagawa M
    • Journal Title

      Endocr

      Volume: 38 Pages: 369-376

    • NAID

      120003338593

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Depressed expression of Klotho and FGFR1 in hyperplastic parathyroid glands from uremic patients.2010

    • Author(s)
      H.Komaba, et al.
    • Journal Title

      Kidney International

      Volume: 77 Pages: 232-238

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] BAMBI gene is epigenetically silenced in a subset of high-grade bladder cancer2009

    • Author(s)
      Sann Sanda Khin, Kitazawa R, Win N, Than TA, Mori K, Kondo T, Kitazawa S
    • Journal Title

      Int J Cancer

      Volume: 125 Pages: 328-338

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Osteosarcoma in a pregnant patient with McCune-Albright syndrome2009

    • Author(s)
      Kanazawa I, Yamauchi M, Yano S. Imanishi Y, Kitazawa R, Nariai Y, Araki A, Kobayashi K, Inaba M, Maruyama R, Yamaguchi T, Sugimoto T
    • Journal Title

      Bone

      Volume: 45 Pages: 603-609

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Thioredoxin-1 overexpression in transgenic mice attenuates streptozotocin-induced diabetic osteopenia2009

    • Author(s)
      Hamada Y, Fujii H, Kitazawa R, Yodoi J, Kitazawa S, Fukagawa M
    • Journal Title

      Bone

      Volume: 44 Pages: 936-941

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Oral charcoal adsorbent(AST-120) prevents progression of cardiac damage in chronic kidney disease through suppression of oxidative stress2009

    • Author(s)
      Fujii H, Nishijima F, Goto S, Sugano M, Yamato H, Kitazawa R, Kitazawa S, Fukagawa M
    • Journal Title

      Nephrol Dial Transplant

      Volume: 24 Pages: 2089-2095

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] BAMBI gene is epigenetically silenced in a subset of high-grade bladder cancer2009

    • Author(s)
      Sann Sanda Khin, et al.
    • Journal Title

      Int J Cancer 125

      Pages: 328-338

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ce promotes intestinal tumorigenesis of ApcMin/+ mice through augmentation of inflammation and angiogenesis2009

    • Author(s)
      Li M., et al.
    • Journal Title

      Carcinogenesis 30

      Pages: 1424-1432

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Thioredoxin-1 overexpression in transgenic mice attenuates streptozotocin-induced diabetic osteopenia2009

    • Author(s)
      Hamada Y., et al.
    • Journal Title

      Bone 44

      Pages: 936-941

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Analysis of Regulatory Mechanism of Mouse RANK Gene Expression through AP-1 Response Element2011

    • Author(s)
      Kitazawa R, Kinto S, et al
    • Organizer
      ASBMR 2011 Annual Meeting
    • Place of Presentation
      San Diego CA, USA
    • Year and Date
      2011-09-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] AP-1応答配列を介するマウスRANK遺伝子発現制御機構の解析2011

    • Author(s)
      金籐聡美, 北澤理子, 他
    • Organizer
      第29回日本骨代謝学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2011-07-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] 破骨細胞分化因子RANKLによる受容体RANKの発現制御機構2011

    • Author(s)
      北澤理子, 向井智美, 他
    • Organizer
      第100回日本病理学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2011-04-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] 破骨細胞分化因子RANKLはNFATを介して受容体RANK発現を促進する2010

    • Author(s)
      北澤理子, 他
    • Organizer
      第99回日本病理学会総会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Year and Date
      2010-04-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] Analysis of Regulatory Mechanism of Mouse RANK Gene Expression through AP-1 Response Element2010

    • Author(s)
      Kitazawa R, Kinto S, Ishii J, Kondo T, Mori K, Kitazawa S
    • Organizer
      ASBMR 2011 Annual Metting
    • Place of Presentation
      San Diego, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] RANKL upregulates mouse RANK gene transcriptionthrough the NFAT binding site of RANK gene promoter2010

    • Author(s)
      Kitazawa R, Ishii J, Mukai S, Kondo T, Mori M, Mori K, Kitazawa S
    • Organizer
      第10回世界骨粗鬆症学会
    • Place of Presentation
      フィレンツェ、イタリア
    • Related Report
      2011 Final Research Report
  • [Presentation] Derepression of mouse SFRP-4 gene expression by oxidative stress : A plausible mechanism leading to low-turnover osteoporosis in diabetes and senescence2010

    • Author(s)
      Mori K, Kitazawa R, Kondo T, Mukai S, Mori M, Kitazawa S
    • Organizer
      第10回世界骨粗鬆症学会
    • Place of Presentation
      フィレンツェ、イタリア
    • Related Report
      2011 Final Research Report
  • [Presentation] Identification and functional analysis of a novel splicing variant of mouse RANK2010

    • Author(s)
      Mukai S, Kitazawa R, Ishii J, Kondo T, Hakozaki A, Horiuchi K, Mori K, Kitazawa S
    • Organizer
      第14回国際内分泌学会
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] マウスRANK遺伝子転写におけるNFATの機能解析2009

    • Author(s)
      北澤理子, 他
    • Organizer
      第98回日本病理学会総会
    • Place of Presentation
      国立京都国際会館(京都府)
    • Year and Date
      2009-05-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] RANKL upregulates mouse RANK gene transcription through the NFAT binding site of its gene promoter2009

    • Author(s)
      Kitazawa R, Ishii J, Mukai S, Kondo T, Mori K, Kitazawa S
    • Organizer
      ASBMR 31st Annual Metting
    • Place of Presentation
      Denver, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] Oxidative DNA damage to methylated CpG located at five bases upstream of TATA-box restores suppressed sFRP-4 gene expression : proposal of a unique mechanism towards diabetic osteoporosis2009

    • Author(s)
      Mori K, Kitazawa R, Fukagawa M, Hamada Y, Kondo T, Kitazawa S
    • Organizer
      ASBMR 31st Annual Metting
    • Place of Presentation
      Denver, USA
    • Related Report
      2011 Final Research Report
  • [Book] 病理と臨床29巻臨時増刊号「病理診断に役立つ分子生物学」第1部-4 DNAシークエンス2011

    • Author(s)
      北澤荘平、森清、近藤武史、北澤理子
    • Publisher
      文光堂
    • Related Report
      2011 Final Research Report
  • [Book] In situ detection of specific gene expression during and immediately after transcription at electron microscopic level. In Microscopy : Science, Technology, Applications and Education2011

    • Author(s)
      S.Kitazawa, et al
    • Total Pages
      200
    • Publisher
      Formatex Research Center, Spain
    • Related Report
      2010 Annual Research Report
  • [Book] 組織細胞化学2010-組織細胞化学イメージングの基礎と最前線:生体内分子局在と機能を探る-2010

    • Author(s)
      北澤荘平, 森清, 近藤武史, 北澤理子
    • Publisher
      日本組織細胞化学会編集
    • Related Report
      2011 Final Research Report
  • [Book] DNA Methylation Research Trends, Epigenetic roles of CpG methylation at non-CpG-islands revealed by morphology-oriented epigenetic research

    • Author(s)
      Kitazawa S, Mori K, Kondo T, Fujimoto M, Kitazawa R
    • Publisher
      Nova
    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.med.kobe-u.ac.jp/patho2/index.html

    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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