Regulatory mechanisms of bone metabolism by innate immune system

• Project/Area Number: 23390426
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Showa University
• Principal Investigator: TAKAMI Masamichi 昭和大学, 歯学部, 教授 (80307058)
• Co-Investigator(Kenkyū-buntansha): KAMIJO Ryutaro 昭和大学, 歯学部, 教授 (70233939) ; TAMURA Tomohiko 横浜市立大学, 医学系研究科, 教授 (50285144)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2012: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2011: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
• Keywords: 自然免疫 / 骨代謝 / 骨粗鬆症 / 細胞分化 / 破骨細胞 / 骨 / 歯周病 / 薬物 / 細胞 / 再生医療 / 骨形成 / マウス / Toll-like receptor / 遺伝子 / 骨吸収

Research Abstract

Activation of Toll-like receptors (TLRs) is thought to exacerbate inflammatory bone resorption. In the present study, we found that Poly(I:C), a synthetic double-stranded RNA (dsRNA) that acts as a ligand of Toll-like receptor 3 (TLR3), suppresses bone loss in osteoporosis model mice, while it inhibited osteoclastogenesis via production of interferon (IFN)-beta and the STAT1- dependent signaling pathway in osteoclast precursors. Thus, Poly(I:C) and TLR3 may be important components of a new therapeutic strategy for inflammatory bone loss.

Research Products

• [Journal Article] Octacalcium phosphate suppresses chondrogenic differentiation of ATDC5 cells. (2013)
  • Author(s): I Shibuya, K Yoshimura, Y Miyamoto, A Yamada, M Takami, T Suzawa, D Suzuki, N Ikumi, F Hiura, T Anada, O Suzuki, R Kamijo.
  • Journal Title: Cell Tissue Res Volume: 352 Issue: 2 Pages: 401-412
  • DOI: 10.1007/s00441-012-1548-8
  • Peer Reviewed
• [Journal Article] Downregulation of carbonic anhydrase IX promotes Col10a1 expression in chondrocytes (2013)
  • Author(s): Maruyama T, Miyamoto Y, Yamamoto G, Yamada A, Yoshimura K, Suzawa T, Takami M, Akiyama T, Hoshino M, Iwasa F, Ikumi N, Tachikawa T, Mishima K, Baba K, Kamijo R
  • Journal Title: PLoS ONE Volume: Vol.8 Issue: 2 Pages: e56984-e56984
  • DOI: 10.1371/journal.pone.0056984
  • Peer Reviewed
• [Journal Article] Development and pharmacological effects of anti-RANKL monoclonal antibody drug Denosumab (2013)
  • Author(s): Takami M
  • Journal Title: Jpn J Clin Immunol Volume: Vol.36 Pages: 162-169
  • NAID: 10031185523
  • URL: https://www.jstage.jst.go.jp/article/jsci/36/3/36_162/_article
• [Journal Article] 抗 RANKL 抗体の開発と臨床応用 (2013)
  • Author(s): 高見正道, 松永朗裕, 稲垣克記, 上條竜太郎
  • Journal Title: THE BONE Volume: 36巻 Pages: 162-169
  • URL: http://www.m-review.co.jp/magazine/detail/J07_27_04
• [Journal Article] 最新の骨粗鬆症学 -骨粗鬆症の最新知見- RANKL とOPG (2013)
  • Author(s): 高見正道
  • Journal Title: 日本臨床 Volume: 71巻 Pages: 150-155
  • URL: https://www.jstage.jst.go.jp/article/jsci/36/3/36_162/_article
• [Journal Article] Development and pharmacological effects of anti-RANKL monoclonal antibody drug Denosumab. (2013)
  • Author(s): Takami M
  • Journal Title: Jpn J Clin Immunol Volume: 36 Pages: 162-169
  • NAID: 10031185523
  • Peer Reviewed
• [Journal Article] 最新の骨粗鬆症学 －骨粗鬆症の最新知見－ RANKLとOPG (2013)
  • Author(s): 高見正道
  • Journal Title: 日本臨牀 Volume: 71 Pages: 150-155
• [Journal Article] 抗 RANKL 抗体の開発と臨床応用 (2013)
  • Author(s): 高見正道、松永朗裕、稲垣克記、上條竜太郎
  • Journal Title: THE BONE Volume: 36 Pages: 162-169
• [Journal Article] Cell adhesion signal regulates RANK expression in osteoclast precursors (2012)
  • Author(s): Mochizuki A, Takami M, Miyamoto Y, Nakamaki T, Tomoyasu S, Kadono Y, Tanaka S, Inoue T, Kamijo R
  • Journal Title: PLoS ONE Volume: 7(11) Issue: 11 Pages: e48795-e48795
  • DOI: 10.1371/journal.pone.0048795
  • Peer Reviewed
• [Journal Article] D-chiro-inositol Negatively Regulates the Formation of Multinucleated Osteoclasts by Down- Regulating NFATc1 (2012)
  • Author(s): Yu J, Choi S, Park ES, Shin B, Yu J, Lee SH, Takami M, Kang JS, Meong H, Rho J
  • Journal Title: J Clin Immunol Volume: 32 Issue: 6 Pages: 1360-1371
  • DOI: 10.1007/s10875-012-9722-z
  • Peer Reviewed
• [Journal Article] R848, a toll-like receptor 7 agonist, inhibits osteoclast differentiation but not survival or bone-resorbing function of mature osteoclasts (2012)
  • Author(s): Miyamoto A, Takami M, Matsumoto A, Mochizuki A, Yamada T, Tachi K, Shibuya I, Nakamach, T, Shioda S, Baba K, Inoue T, Miyamoto Y, Yim M, Kamijo R
  • Journal Title: Cytotechnology Volume: 64 Issue: 3 Pages: 331-339
  • DOI: 10.1007/s10616-012-9442-5
  • Peer Reviewed
• [Journal Article] BMP2 differentially regulates the expression of Gremlin1 and Gremlin2, the negative regulators of BMP function, during osteoblast differentiation (2012)
  • Author(s): Suzuki D, Yamada A, Aizawa R, Funato S, Matsumoto T, Suzuki W, Takami M, Miyamoto Y, Suzawa T, Yamamoto M, Baba K, Kamijo R
  • Journal Title: Calcif Tissue Int Volume: 91 Issue: 1 Pages: 88-96
  • DOI: 10.1007/s00223-012-9614-5
  • Peer Reviewed
• [Journal Article] Suppressive Effects of the Leaf of Terminalia catappa L. on Osteoclast Differentiation In Vitro and Bone Weight Loss In Vivo (2012)
  • Author(s): Koyama T, Nakajima C, Nishimoto S, Takami, M, Woo J-T, Yazawa K
  • Journal Title: J Nutr Sci Vitaminol Volume: 58 Pages: 129-135
  • NAID: 130002103030
  • URL: https://www.jstage.jst.go.jp/article/jnsv/58/2/58_129/_article
  • Peer Reviewed
• [Journal Article] Nephronectin expression is regulated by SMAD signaling in osteoblast-like MC3T3-E1 cells (2012)
  • Author(s): Tsukasaki M, Yamada A, Yoshimura K, Miyazono A, Yamamoto M, Takami M, Miyamoto Y, Morimura N, Kamijo R
  • Journal Title: Biochem Biophys Res Commun Volume: 425 Issue: 2 Pages: 390-392
  • DOI: 10.1016/j.bbrc.2012.07.106
  • Peer Reviewed
• [Journal Article] 骨吸収抑制剤デノスマブ (2012)
  • Author(s): 高見正道
  • Journal Title: 骨粗鬆症治療 Volume: 11 Pages: 34-41
  • URL: http://mol.medicalonline.jp/library/journal/download?GoodsID=ae6kotue/2012/001103/007&name=0190-0197j&UserID=202.254.227.190
• [Journal Article] インターフェロン制御因子(IRF-8)による破骨細胞形成抑制を介した骨代謝調節 (2012)
  • Author(s): 高見正道
  • Journal Title: 炎症と免疫 Volume: 20 Pages: 68-73
  • URL: http://www.sentan.com/cgi-bin/db_n.cgi?mode=view_backno&no=880
• [Journal Article] Shared and distinct functions of the transcription factors IRF4 and IRF8 in myeloid cell development (2011)
  • Author(s): Yamamoto M, et al
  • Journal Title: PLoS ONE Volume: 6 Issue: 10 Pages: e25812-e25812
  • DOI: 10.1371/journal.pone.0025812
  • Peer Reviewed
• [Journal Article] Splenic extramedullary hemopoiesis caused by a dysfunctional mutation inthe (2011)
  • Author(s): Shinzawa M., Maruyama Y., Qin J., Akiyama N., Miyauchi M., Yanai H., Takami M., Inoue J., and Akiyama T*(corresponding author).
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 414 Issue: 4 Pages: 773-778
  • DOI: 10.1016/j.bbrc.2011.10.001
  • Peer Reviewed
• [Journal Article] Identification and isolation of neural crest derived cells in nasal concha (2011)
  • Author(s): Ono M, Takami M, Suzawa T, Miyauchi T, Ogasawara A, Yamada A, Hosono T, Ararta S, Miyamoto Y, Baba K, Nakamura M, Osumi N, Maki K, Kamijo R
  • Journal Title: Jpn J Tissue Cult Dent Res Volume: 20 Pages: 29-35
  • Peer Reviewed
• [Journal Article] Expression of POEM, a positive regulator of osteoblast differentiation, is suppressed by TNF-α (2011)
  • Author(s): Tsukasaki M, et al
  • Journal Title: Biochem Biophys Res Commun Volume: 410 Issue: 4 Pages: 766-770
  • DOI: 10.1016/j.bbrc.2011.06.048
  • Peer Reviewed
• [Journal Article] Feedback inhibition of osteoclastogenesis during inflammation by IL-10, M-CSF receptor shedding, and induction of IRF8 (2011)
  • Author(s): Ivashkiv LB, Zhao B, Park-Min KH, Takami M
  • Journal Title: Ann N Y Acad Sci Volume: 1237 Issue: 1 Pages: 88-94
  • DOI: 10.1111/j.1749-6632.2011.06217.x
  • Peer Reviewed
• [Journal Article] Monocarboxylate transporter-1 is required for cell death in mouse chondrocytic ATDC5 cells exposed to interleukin-1β via activation of nuclear factor-κB and expression of phagocyte-type NADPH-oxidase (2011)
  • Author(s): Yoshimura K, et al
  • Journal Title: J Biol Chem Volume: 286 Issue: 17 Pages: 14744-14752
  • DOI: 10.1074/jbc.m111.221259
  • Peer Reviewed
• [Presentation] Effects of TGF-β1 and LPS on BMP-2-induced ectopic bone formation (2013)
  • Author(s): Akifumi Matsumoto, Masamichi Takami, Keita Tachi, Kazuyoshi Baba, Ryutaro Kamijo
  • Organizer: 2nd Joint Meeting of the International Bone and Mineral Society and The Japanese Society for Bone and Mineral Research
  • Place of Presentation: 神戸
• [Presentation] 菌体成分がBMP-2 とTGF-β1 が誘導する異所性骨形成に与える影響とそのメカニズム (2013)
  • Author(s): 松本光史, 高見正道, 舘慶太, 上條竜太郎, 馬場一美
  • Organizer: 公益社団法人日本補綴歯科学会第122回学術大会
  • Place of Presentation: 福岡
• [Presentation] TGF-β1 と菌体がBMP-2 の異所性骨形成誘導に及ぼす影響 (2013)
  • Author(s): 松本光史, 高見正道, 舘慶太, 馬場一美, 上條竜太郎
  • Organizer: 第68回NPO法人日本口腔科学会学術集会
  • Place of Presentation: 宇都宮
• [Presentation] 神経堤由来の毛包細胞を用いた骨芽細胞分化誘導 (2013)
  • Author(s): 森澤絵里, 高見正道, 須澤徹夫, 馬場一美, 大隅典子, 上條竜太郎
  • Organizer: 第68回NPO法人日本口腔科学会学術集会
  • Place of Presentation: 宇都宮
• [Presentation] 毛包に存在する神経堤由来細胞を用いた骨芽細胞の分化誘導 (2013)
  • Author(s): 森澤絵里, 高見正道, 須澤徹夫, 上條竜太郎, 馬場一美
  • Organizer: 公益社団法人日本補綴歯科学会第122回学術大会
  • Place of Presentation: 福岡
• [Presentation] Characterization of osteoclast precursors in bone marrow, blood, and spleen (2013)
  • Author(s): Takuya Enomoto, Masamichi Takami, Yoichi Miyamoto, Matsuo Yamamoto, and Ryutaro Kamijo
  • Organizer: 2nd meeting of the International Association for Dental Research Asia Pacific Region (IADR-APR)
  • Place of Presentation: バンコク(タイ)
• [Presentation] 毛包に存在する神経堤由来細胞を用いた骨芽細胞分化誘導 (2013)
  • Author(s): 森澤絵里, 高見正道, 須澤徹夫, 上條竜太郎, 馬場一美
  • Organizer: 第2回補綴若手研究会
  • Place of Presentation: 岡山
• [Presentation] 菌体成分がBMP-2とTGF-β1が誘導する異所性骨形成に与える影響とそのメカニズム (2013)
  • Author(s): 松本光史, 高見正道, 舘慶太, 上條竜太郎, 馬場一美
  • Organizer: 公益社団法人日本補綴歯科学会第122回学術大会
  • Place of Presentation: 福岡
• [Presentation] TGF-β1と菌体がBMP-2の異所性骨形成誘導に及ぼす影響 (2013)
  • Author(s): 松本光史，高見正道，舘慶太，馬場一美，上條竜太郎
  • Organizer: 第68回NPO法人日本口腔科学会学術集会
  • Place of Presentation: 宇都宮
• [Presentation] Characterization of osteoclast precursors in bone marrow, blood, and spleen (2013)
  • Author(s): Takuya Enomoto, Masamichi Takami, Yoichi Miyamoto, Matsuo Yamamoto, and Ryutaro Kamijo
  • Organizer: 2nd meeting of the International Association for Dental Research Asia Pacific Region (IADR-APR)
  • Place of Presentation: バンコク（タイ）
• [Presentation] 毛包に存在する神経堤由来細胞を用いた骨芽細胞分化誘導 (2013)
  • Author(s): 森澤絵里
  • Organizer: 第２回補綴若手研究会
  • Place of Presentation: 岡山
• [Presentation] TGF-β1 およびLPS がBMP 誘導性の骨形成に及ぼす影響 (2012)
  • Author(s): 松本光史, 高見正道, 舘慶太, 上條竜太郎, 馬場一美
  • Organizer: 第15回骨発生・再生研究会
  • Place of Presentation: 埼玉
  • Year and Date: 2012-11-10
• [Presentation] TLR3 リガンドPoly(I : C)による骨吸収抑制 (2012)
  • Author(s): 高見正道
  • Organizer: 第12回東京骨関節フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2012-07-24
• [Presentation] Roles of innate immune system in bone metabolism (2012)
  • Author(s): Masamichi Takami
  • Organizer: 9th Bone Biology Forum
  • Place of Presentation: 静岡
• [Presentation] LPS Inhibits Ectopic Bone Formation Induced by BMP-2 plus TGF-β1 in Mice (2012)
  • Author(s): Akifumi Matsumoto, Masamichi Takami, Keita Tachi, Kazuyoshi Baba, Ryutaro Kamijo
  • Organizer: 2012 Annual Meeting of The American Society for Bone and Mineral Research
  • Place of Presentation: ミネアポリス(米国)
• [Presentation] TLR3リガンドPoly(I:C)による骨吸収抑制 (2012)
  • Author(s): 高見正道
  • Organizer: 第12回 東京骨関節フォーラム
  • Place of Presentation: 東京
• [Presentation] TGF-β1 およびLPSがBMP誘導性の骨形成に及ぼす影響 (2012)
  • Author(s): 松本光史
  • Organizer: 第15回骨発生・再生研究会
  • Place of Presentation: 埼玉
• [Presentation] LPS Inhibits Ectopic Bone Formation Induced by BMP-2 plus TGF-β1 in Mice (2012)
  • Author(s): Akifumi Matsumoto
  • Organizer: 2012 Annual Meeting of The American Society for Bone and Mineral Research
  • Place of Presentation: ミネアポリス（米国）
• [Presentation] 顎口腔組織における神経堤細胞の新所見 (2011)
  • Author(s): 高見正道
  • Organizer: 歯科基礎医学会サテライトシンポジウム
  • Place of Presentation: 岐阜(招待講演)
  • Year and Date: 2011-09-30
• [Presentation] Double stranded RNA increases bone mass in osteoporosis model mice by inhibiting osteoclastogenesis via interferon-β/STAT1 pathway (2011)
  • Author(s): Miyamoto A, et al
  • Organizer: IOF-ANZBMR
  • Place of Presentation: Gold Coast, Australia
• [Presentation] 二本鎖RNAアナログはインターフェロンβ/STAT1経路を介して破骨細胞分化を抑制し骨粗鬆症モデル動物の骨量を増加させる (2011)
  • Author(s): 宮本阿礼, 他
  • Organizer: 第29回日本骨代謝学会学術集会
  • Place of Presentation: 大阪
• [Presentation] 成体における神経堤由来細胞の分布とそれを用いた骨芽細胞の分化誘導 (2011)
  • Author(s): 小野美樹, 他
  • Organizer: 第29回日本骨代謝学会学術集会
  • Place of Presentation: 大阪
• [Presentation] Distribution of neural crest-derived cells in adult mice and their induction into osteoblastic cells (2011)
  • Author(s): Ono M, et al
  • Organizer: The 33th Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: San Diego, California, USA
• [Presentation] Double stranded RNA increases bone mass in osteoporosis model mice by inhibiting osteoclastogenesis via interferon-β/STAT1 pathway (2011)
  • Author(s): Miyamoto A, et al
  • Organizer: The 33th Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: San Diego, California, USA
• [Presentation] 二本鎖RNAアナログはインターフェロンβ/STAT1経路を介して破骨細胞分化を抑制し骨粗鬆症モデル動物の骨量を増加させる (2011)
  • Author(s): 宮本阿礼, 他
  • Organizer: 第53回歯科基礎医学会学術大会
  • Place of Presentation: 岐阜
• [Book] Functions of Toll-like receptors in osteoclast differentiation induced by receptor activator of NF-κB ligand. In The New Frontiers in Research for Oral Cancer (2013)
  • Author(s): Takami M, Miyamoto Y, Matsumoto A, Mochizuki A, Tachi K, Baba K, Inoue T, Mijung Y, Shibuya I, Zhao B, Kamijo R
  • Total Pages: 209
  • Publisher: MARUZEN. CO. LTD, Tokyo
  • URL: http://iss.ndl.go.jp/books/R100000002-I024260969-00
• [Book] Screening for regulators of osteoblast differentiation induced by BMP-2. The New Frontiers in Research for Oral Cancer (2013)
  • Author(s): Yamada A, Matsumoto T, Suzuki D, Funato S, Takami M, Aizawa R, Suzawa T, Miyamoto Y, Suzuki W, Yoshimura K, Nakayama M, Maki K, Yamamoto M, Baba K, Kamijo R
  • Total Pages: 209
  • Publisher: MARUZEN. CO. LTD, Tokyo
  • URL: http://iss.ndl.go.jp/books/R100000002-I024260969-00
• [Book] The New Frontiers in Oral Cancer (2012)
  • Author(s): Masamichi Takami
  • Total Pages: 209
  • Publisher: Maruzen Planet
• [Remarks]
  • URL: http://www10.showa-u.ac.jp/~oralbio/publications.html
• [Remarks] 昭和大学歯学部口腔生化学講座
  • URL: http://www10.showa-u.ac.jp/~oralbio/publications.html
• [Remarks] 昭和大学歯学部口腔生化学講座
  • URL: http://www10.showa-u.ac.jp/~oralbio/index.html