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2012 Fiscal Year Final Research Report

Enhancement of the BMP-induced bone formation by the inhibition of NF-κB based on genetic evidence

Research Project

  • PDF
Project/Area Number 22592042
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionKyushu Dental College

Principal Investigator

ZHANG Min  九州歯科大学, 歯学部, 助教 (00326472)

Co-Investigator(Kenkyū-buntansha) KOU Matsuo  九州歯科大学, 歯学部, 准教授 (70238971)
JIMI Eijiro  九州歯科大学, 歯学部, 教授 (40276598)
Project Period (FY) 2010 – 2012
Keywords骨再生 / NF-κB / 骨芽細胞 / BMP / 骨代謝
Research Abstract

We previously reported that alymphoplasia (aly/aly) mice, which have a natural loss-of-function mutation in the Nik gene, which encodes a kinase essential for the processing of p100 to p52 in the alternative nuclear factor-κB (NF-κB) pathway, show mild osteopetrosis with an increase in several parameters of bone formation: bone formation rate, mineral apposition rate, and osteoblast number. We therefore investigated the molecular mechanisms triggered by the alternative NF-κB pathway in the regulation of osteoblast differentiation using primary osteoblasts (POB) prepared from aly/aly mice. Alkaline phosphatase (ALP) activity and mineralization induced by the presence of β-glycerophosphate and ascorbic acid were enhanced in POB from aly/aly compared with wild-type (WT) mice. Furthermore, osteoblastic differentiation induced by bone morphogenetic protein 2 (BMP2), as shown by ALP activity, mRNA expression of osteocalcin, Id1, Osterix and Runx2, and Sma- and Mad-related protein (Smad)1/5/8 phosphorylation, was also enhanced in POB from aly/aly mice. The ectopic bone formation in vivo that was induced by BMP2 was enhanced in aly/aly mice compared with controls. Transfection of a mutant form of p100, p100ΔGRR, which cannot be processed to p52, stimulated ALP activity and Smad phosphorylation. In contrast to p100ΔGRR, overexpression of p52 inhibited these events. Both BMP2-induced ALP activity and Smad phosphorylation were reduced in POB from p100-deficient mice, which carry a homozygous deletion of the COOH-terminal ankyrin repeats of p100 but still express functional p52 protein. p52 and p100ΔGRR interacted with a BMP receptor, ALK2, in overexpressed COS7 cells and changed the ALK2 protein levels in opposite directions: p52 reduced ALK2 and p100 increased it. Thus, the alternative the NF-κB pathway via the processing of p52 from p100 negatively regulates osteoblastic differentiation and bone formation by modifying BMP activity.

  • Research Products

    (23 results)

All 2012 2011 2010

All Journal Article (9 results) Presentation (14 results)

  • [Journal Article] The current and future therapies of bone regeneration to repair bone defects2012

    • Author(s)
      Jimi E, Hirata S, Osawa K, Terashita M, Kitamura C, Fukushima H
    • Journal Title

      Int J Dentistry

      Volume: 148261

    • DOI

      DOI:10.1155/2012/148261.

  • [Journal Article] Clinical Discussion Regarding Replantation of a Detached Tooth- Long-lterm follow-up of immature permanent tooth2012

    • Author(s)
      Tadashi Yoshida, Fumio Soga, Min Zhang.
    • Journal Title

      J Assoc Dent traumatol

      Volume: 8(1) Pages: 68-74

  • [Journal Article] Magnetic resonance angiography with fresh blood imaging for identication of hemangiomas and blood vessels around hemangiomas in oral and maxillofacial regions2012

    • Author(s)
      MOda,T Tanaka, SKito,S Matsumoto-Takeda, K Otsuka, Y Hayashi, N Wakasugi-Sato,I Yoshioka,M Habu, S Kokuryo,M Kodama,S Nogami, I Miyamoto, N Yamamoto, A Ishikawa, M Zhang,K Matsuo, S Shiiba, Y Seta, Y Yamashita,TTakahashi,KTominaga,Ymorimoto
    • Journal Title

      Oral Surg Oral Med Oral Pathol Oral Radiol

      Volume: 113(4) Pages: 559-566

    • DOI

      DOI:org/10.1016/j.0000.2011.10.003.

  • [Journal Article] Accumulation of p100, a precursor of NF-κB2011

    • Author(s)
      SeoY, Fukushima H, Maruyama T, Nakao Kuroishi K, Osawa K, Nagano K, Aoki K, Weih F, Doi T, Zhang M, Ohya K, Katagiri T, Hosokawa R, Jimi E.
    • Journal Title

      enhances osteoblastic differentiation in vitroand bone formation in vivoin aly/alymice Mol Endocrinol

      Volume: 26 Pages: 414-422

    • DOI

      DOI:10.1210/me.2011-1241

  • [Journal Article] Involvement of PRIP, phospholipase C-related, but catalytically inactive protein, in bone formation.2011

    • Author(s)
      Tsutsumi K, Matsuda M, Kotani M, Mizokami A, Murakami A, Takahashi I, Terada Y, Kanematsu T, Fukami K, Takenawa T, Jimi E, Hirata M
    • Journal Title

      J Biol Chem

      Volume: 286 Pages: 31032-31042

    • DOI

      DOI:10.1074/jbc.M111.235903

  • [Journal Article] a proteasome inhibitor, enhances BMP-induced osteoblastic differentiation by increasing active Smads2011

    • Author(s)
      Ito Y, Fukushima H, Katagiri T, Seo Y, Hirata S, Zhang M, Hosokawa R, Jimi E. Lactacystin
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 407 Pages: 225-229.

    • DOI

      DOI:10.1016/j.bbrc.2011.03.003.

  • [Journal Article] Leiomyomatous hamartoma of themidline maxillary gingival presenting as a congenital epulis:A case report with an immunohistochemical study2011

    • Author(s)
      ZhangM,matsuo K,Yamashita Y,Takahashi T
    • Journal Title

      In JOral and Maxillofac Surg

      Volume: 40 Pages: 1322-1326

    • DOI

      DOI:10.1016/j.ijom.2011.05.009.

  • [Journal Article] Promoting effects of thymosin β4 on granulation tissue and new bone formation after tooth extraction in rats2011

    • Author(s)
      K Matsuo,Y Akasaki, K Adachi,M Zhang, A Ishikawa,E Jimi,T Nishihara, R Hosokawa
    • Journal Title

      Oral Surg Oral Med Oral Pathol Oral Radiol

      Volume: 114 Pages: 17-26

    • DOI

      DOI:org/10.1016/j.tripleo.2011.05.025

  • [Journal Article] Ohnishi K,Matsuo K.Immunohistochemical study of the ED1 antibody in wound healing and dentin bridge formation after pulpotomy in the rat molar2010

    • Author(s)
      Zhang M, Asano K
    • Journal Title

      J AssocDent Traumatol

      Volume: 6(1) Pages: 28-35

  • [Presentation] 糖尿病性歯周炎発症における骨吸収の分子機構の解明2012

    • Author(s)
      張 皿、大澤賢司、松尾拡、福島秀文、自見 英治郎
    • Organizer
      第54回歯科基礎医学会奥羽大学
    • Place of Presentation
      福島
    • Year and Date
      2012-09-15
  • [Presentation] NF-κB2 のp100 のプロセシングは骨代謝において重要である2012

    • Author(s)
      大澤賢次、福島秀文、Alles Neil、青木和広、張 皿、大谷啓一、自見英治郎
    • Organizer
      日本歯科基礎医学会,奥羽大学
    • Place of Presentation
      福島
    • Year and Date
      2012-09-15
  • [Presentation] Clinical Problemを見据えた転写因子NF-κBによる骨代謝調節機構の解明2012

    • Author(s)
      自見英治郎
    • Organizer
      日本歯科基礎医学会,奥羽大学
    • Place of Presentation
      福島
    • Year and Date
      2012-09-15
  • [Presentation] 糖尿病性歯周炎発症の分子機構の解明と治療薬開発のための基礎研究2012

    • Author(s)
      張 皿、松尾拡、中道郁夫、自見 英治郎
    • Organizer
      九州歯学会
    • Place of Presentation
      九歯大
    • Year and Date
      2012-05-19
  • [Presentation] NF-κB非古典的経路による骨形成の抑制2011

    • Author(s)
      妹尾吉訓、福島秀文、片桐岳信、青木和広、永野健一、大谷啓一、細川隆司、自見英治郎
    • Organizer
      第53回歯科基礎医学会学術大会
    • Place of Presentation
      岐阜
    • Year and Date
      20110930-1002
  • [Presentation] 効率的な骨再生を目指したBMPシグナル増強因子の探索2011

    • Author(s)
      自見英治郎、平田志津、福島秀文、寺下正道、北村知昭
    • Organizer
      第71回九州歯科学会総会
    • Year and Date
      20110528-29
  • [Presentation] Immunohistochemical Study of CGRP and Immunocompetent Cells in Wound Healing Following Rat Molar Pulpotomy2011

    • Author(s)
      M Zhang
    • Organizer
      he 5thConference of Asian International Association of Dental Traumatology. Sept.4
    • Place of Presentation
      Aichi Gakuin University, Nagoya, Japan.
    • Year and Date
      20110000
  • [Presentation] 転写因子NF-κBによる骨形成抑制機構2011

    • Author(s)
      自見英治郎
    • Organizer
      徳島大学大学院ヘルスバイオサイエンス研究部『医療系クラスターによる組織的大学院教育』の「骨とCaクラスター」ミニリトリート
    • Place of Presentation
      兵庫
    • Year and Date
      2011-12-10
  • [Presentation] aly/alyマウスにおける骨形成メカニズムの解明2010

    • Author(s)
      妹尾 吉訓、福島 秀文、片桐 岳信、青木 和広、永野 健一、大谷 啓一、細川隆司、 自見 英治郎
    • Organizer
      第52回歯科基礎医学会学術大会ならびに総会
    • Place of Presentation
      タワーホール船堀 船堀 千葉
    • Year and Date
      20100920-22
  • [Presentation] aly/alyマウスではBMPによるSmad1/5/8のリン酸化が亢進することで骨形成が亢進する2010

    • Author(s)
      自見英治郎、片桐岳信、永野健一、青木和広、大谷啓一、福島秀文
    • Organizer
      第28回日本骨代謝学会学術集会
    • Place of Presentation
      京王プラザホテル東京
    • Year and Date
      20100721-23
  • [Presentation] Response of immunocompetent cells in dentin bridge formation after pulpotomy2010

    • Author(s)
      M Zhang, E Jimi and K Matsuo
    • Organizer
      JADR
    • Place of Presentation
      Kyushu Dental University.
    • Year and Date
      2010-11-21
  • [Presentation] Immunohistochemical study of ED1 antibody in wound healing and dentin bridge formation after pulpotomy in rat molar2010

    • Author(s)
      M Zhang, K Matsuo, T Tanaka
    • Organizer
      第10回日本外傷歯学会
    • Place of Presentation
      アクロス福岡国際会議場福岡.
    • Year and Date
      2010-11-14
  • [Presentation] TNFαはNF-κBの活性化を介してBMP2による骨芽細胞分化を抑制する2010

    • Author(s)
      自見 英治郎
    • Organizer
      第13回骨発生、再生研究会
    • Place of Presentation
      慶応義塾大学医学部総合医科学研究棟 東京
    • Year and Date
      2010-11-13
  • [Presentation] 女児の上顎正中部歯肉に発現したいわゆる平滑筋性過誤腫の1例2010

    • Author(s)
      張皿、松尾拡、山下善弘、山本哲彰、高橋哲
    • Organizer
      西日本臨床小児口腔外科学会
    • Place of Presentation
      大阪大学
    • Year and Date
      2010-10-03

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Published: 2014-08-29  

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