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Applied research of periodontal disease therapeutics using osteogenic sugnal from osteoclasts

Research Project

Project/Area Number 16H05508
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionMatsumoto Dental University

Principal Investigator

Udagawa Nobuyuki  松本歯科大学, 歯学部, 教授 (70245801)

Co-Investigator(Kenkyū-buntansha) 小出 雅則  松本歯科大学, 総合歯科医学研究所, 講師 (10367617)
中道 裕子  松本歯科大学, 総合歯科医学研究所, 講師 (20350829)
中村 美どり  松本歯科大学, 歯学部, 准教授 (90278177)
上原 俊介  松本歯科大学, 歯学部, 講師 (90434480)
溝口 利英  松本歯科大学, 総合歯科医学研究所, 講師 (90329475)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords破骨細胞 / 骨芽細胞 / 骨細胞 / オステオプロテゲリン / スクレロスチン / 白血病抑制因子 / 骨吸収 / 歯周病 / 骨代謝共役 / 骨形成 / RANKL / OPG / リバースシグナル / 骨リモデリング
Outline of Final Research Achievements

Osteoprotegerin (OPG) strongly inhibits osteoclast differentiation. We demonstrate that osteoprotegerin (OPG) and sclerostin produced by osteocytes is play an important role in the maintenance of cortical bone and alveolar bone, from experimental results using osteoprotegerin (OPG) gene-deficient mice. In addition, osteoclast-derived LIF (leukemia inhibitory factor) has been shown to reduce sclerostin expression in bone cells and to promote bone formation.

Academic Significance and Societal Importance of the Research Achievements

破骨細胞と骨細胞間のシグナル伝達解析は、骨代謝研究の中で現在最も注目されている研究である。破骨細胞からの骨形成促進シグナルを解明するという視点は、独創的であると考える。本研究は、新しい歯周病治療薬へ応用開発する糸口を見出すことを目的として計画され、今回得られた知見は、歯周病および骨粗鬆症治療に新しい指針を提供するものである。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (22 results)

All 2018 2017 2016 2015

All Journal Article (13 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 13 results,  Open Access: 11 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results) Book (1 results)

  • [Journal Article] Coupling of bone resorption and formation by RANKL reverse signalling.2018

    • Author(s)
      Ikebuchi Y, Aoki S, Honma M, Hayashi M, Sugamori Y, Khan M, Kariya Y, Kato G, Tabata Y, Penninger JM, Udagawa N, Aoki K, Suzuki H
    • Journal Title

      Nature

      Volume: 561 Issue: 7722 Pages: 195-200

    • DOI

      10.1038/s41586-018-0482-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mechanisms involved in bone resorption regulated by vitamin D2018

    • Author(s)
      Nakamichi Yuko、Udagawa Nobuyuki、Suda Tatsuo、Takahashi Naoyuki
    • Journal Title

      The Journal of Steroid Biochemistry and Molecular Biology

      Volume: 177 Pages: 70-76

    • DOI

      10.1016/j.jsbmb.2017.11.005

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Non-canonical Wnt signals regulate cytoskeletal remodeling in osteoclasts.2018

    • Author(s)
      Uehara S, Udagawa N, Kobayashi Y
    • Journal Title

      Cell Mol Life Sci

      Volume: 75 Issue: 20 Pages: 3683-3692

    • DOI

      10.1007/s00018-018-2881-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Olfactomedin-like protein OLFML1 inhibits Hippo signaling and mineralization in osteoblasts.2018

    • Author(s)
      Murakami K, Kikugawa S, Kobayashi Y, Uehara S, Suzuki T, Kato H, Udagawa N, Nakamura Y
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 28 Issue: 2 Pages: 419-425

    • DOI

      10.1016/j.bbrc.2018.09.112

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 歯周治療の動脈硬化症指標(Cardio Ankle Vascular Index: CAVI)に対する効果2018

    • Author(s)
      守安攝子, 長岡 香, 中澤恵美子, 福満典子, 中村美どり, 荒 敏昭, 吉成伸夫, 宇田川信之, 矢ヶ﨑 雅
    • Journal Title

      松本歯学

      Volume: 44 Pages: 79-87

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protein kinase N3 promotes bone resorption by osteoclasts in response to Wnt5a-Ror2 signaling.2017

    • Author(s)
      Uehara S, Udagawa N, Mukai H, Ishihara A, Maeda K, Yamashita T, Murakami K, Nishita M, Nakamura T, Kato S, Minami Y, Takahashi N and Kobayashi Y
    • Journal Title

      Sci Signal

      Volume: 10 Issue: 494

    • DOI

      10.1126/scisignal.aan0023

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] VDR in osteoblast-lineage cells primarily mediates vitamin D treatment-iInduced increase in bone mass by suppressing bone resorption.2017

    • Author(s)
      Nakamichi Y, Udagawa N, Horibe K, Mizoguchi T, Yamamoto Y, Nakamura T, Hosoya A, Kato S, Suda T, Takahashi N
    • Journal Title

      J Bone Miner Res

      Volume: 32 Issue: 6 Pages: 1297-1308

    • DOI

      10.1002/jbmr.3096

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The W9 peptide directly stimulates osteoblast differentiation via RANKL signaling.2017

    • Author(s)
      Nakamura M, Nakamichi Y, Mizoguchi T, Koide M, Yamashita T, Ara T, Nakamura H, Penninger JM, Furuya Y, Yasuda H and Udagawa N
    • Journal Title

      Journal of Oral Biosciences

      Volume: 59 Pages: 146-151

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Platypus and opossum calcitonins exhibit strong activities, even though they belong to mammals.2017

    • Author(s)
      Yamashita T, Udagawa N, Thirukonda GJ, Uehara S, Yamauchi H, Suzuki N, Li F, Kobayashi Y, Takahashi N.
    • Journal Title

      Gen Comp Endocrinol.

      Volume: 246 Pages: 270-278

    • DOI

      10.1016/j.ygcen.2017.01.001

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Osteogenic Factor Runx2 Marks a Subset of Leptin Receptor-Positive Cells that Sit Atop the Bone Marrow Stromal Cell Hierarchy2017

    • Author(s)
      Yang Mengyu、Arai Atsushi、Udagawa Nobuyuki、Hiraga Toru、Lijuan Zhao、Ito Susumu、Komori Toshihisa、Moriishi Takeshi、Matsuo Koichi、Shimoda Kouji、Zahalka Ali H.、Kobayashi Yasuhiro、Takahashi Naoyuki、Mizoguchi Toshihide
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 4928-4928

    • DOI

      10.1038/s41598-017-05401-1

    • NAID

      120006576162

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Angiotensin II stimulation of cardiac hypertrophy and functional decompensation in osteoprotegerin-deficient mice.2016

    • Author(s)
      Tsuruda T, Sekita-Hatakeyama Y, Hao Y, Sakamoto S, Kurogi S, Nakamura M, Udagawa N, Funamoto T, Sekimoto T, Hatakeyama K, Chosa E, Kato J, Asada Y, Kitamura K.
    • Journal Title

      Hypertension

      Volume: 67 Issue: 5 Pages: 848-856

    • DOI

      10.1161/hypertensionaha.115.06689

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Peptide drugs accelerate BMP-2-induced calvarial bone regeneration and stimulate osteoblast differentiation through mTORC1 signaling.2016

    • Author(s)
      Sugamori Y, Mise-Omata S, Maeda C, Aoki S, Tabata Y, Murali R, Yasuda H, Udagawa N, Suzuki H, Honma M, Aoki K.
    • Journal Title

      Bioessays

      Volume: 38 Issue: 8 Pages: 717-725

    • DOI

      10.1002/bies.201600104

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The regulation of osteoclast differentiation by Wnt signals2015

    • Author(s)
      Kobayashi Y, Uehara S, Koide M, Takahashi N
    • Journal Title

      Bonekey Rep

      Volume: 4 Issue: 4 Pages: 713-713

    • DOI

      10.1093/jb/mvv124

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 臓器年齢と酸化ストレス-破骨細胞研究からの骨年齢-2018

    • Author(s)
      宇田川信之
    • Organizer
      日本抗加齢学会総会 (第18回)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 骨改造制御の新局面:骨吸収から骨形成・骨再生への橋渡し機構を探る-破骨細胞の骨形成シグナルにおける重要性-2018

    • Author(s)
      宇田川信之
    • Organizer
      歯科基礎医学会学術大会(第60回)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 骨はダイナミックに躍動している2018

    • Author(s)
      宇田川信之
    • Organizer
      日本歯科理工学会中部地方会夏期セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 歯槽骨の骨リモデリングにおける骨細胞の役割2018

    • Author(s)
      小出雅則, 宇田川信之
    • Organizer
      日本骨代謝学会学術集会 (第36回)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) plays important roles in the induction of both bone-resorbing activity of osteoclasts and osteoblast differentiation2018

    • Author(s)
      Udagawa N, Koide M, Uehara S, Arai A, Mizoguchi T, Yamashita T, Nakamura M, Kobayashi Y, Takahashi N, Kumakura S, Fukuda C, Tsuda E
    • Organizer
      The American Society for Bone and Mineral Research (ASBMR) 2018 Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Anti-Siglec-15 antibody inhibits bone-resorbing activity of osteoclasts and stimulates osteoblast differentiation.2017

    • Author(s)
      Udagawa N, Uehara S, Koide M, Arai A, Mizoguchi T, Nakamura M, Kobayashi Y, Takahashi N, Fukuda C, Tsuda E
    • Organizer
      The American Society for Bone and Mineral Research (ASBMR) 2017 Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] W9 ペプチドのヒト破骨細胞分化抑制作用と骨芽細胞分化促進作用2016

    • Author(s)
      中村美どり,小出雅則,山下照仁,小林泰浩,高橋直之,宇田川信之
    • Organizer
      歯科基礎医学会学術大会(第58回)
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Year and Date
      2016-08-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] カテプシンK阻害剤投与は、オステオプロテゲリン欠損マウスにおいて、骨吸収抑制と共に骨形成促進作用を示す2016

    • Author(s)
      中村美どり, 中道裕子, 溝口利英, 小林泰浩, 高橋直之, 宇田川信之
    • Organizer
      日本骨代謝学会学術集会 (第34回)
    • Place of Presentation
      大阪国際会議場(大阪府)
    • Year and Date
      2016-07-20
    • Related Report
      2016 Annual Research Report
  • [Book] 高齢者への歯周治療と口腔管理2018

    • Author(s)
      宇田川信之,小出雅則,中村美どり, 尾崎友輝, 吉成伸夫
    • Total Pages
      283
    • Publisher
      インターアクション社
    • ISBN
      9784909066053
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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