Immunological approaches to the mechanisms of bisphosphonate-related osteonecrosis of the jaw

• Project/Area Number: 21592511
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Hokkaido University
• Principal Investigator: DEYAMA Yoshiaki 北海道大学, 大学院・歯学研究科, 准教授 (80271667)
• Co-Investigator(Kenkyū-buntansha): TOTSUKA Yasunori 北海道大学, 大学院・歯学研究科, 教授 (00109456) ; YASUDA Motoaki 北海道大学, 大学院・歯学研究科, 准教授 (90239765) ; IIZUKA Tadashi 北海道大学, 大学院・歯学研究科, 准教授 (80168062) ; YOSHIMURA Yoshitaka 北海道大学, 大学院・歯学研究科, 助教 (30230816)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ビスホスホネート / 顎骨壊死 / 免疫 / ビスホスフォネート / マクロファージ / 免疫細胞

Research Abstract

In this study, we investigated the effects of bisphosphonate on osteoclasts and their precursor cells to clarify one of the mechanisms of bisphosphonate-related osteonecrosis of the jaw(BRONJ). BRONJ-related bisphosphonates strongly inhibited osteoclastogenesis and bone resorption activity. On the other hand, they showed cytotoxicity and enhanced microbial pathogens-induced cell death.

Research Products

• [Journal Article] Toll like receptor 5 ligand induces monocyte chemoattractant protein-1 in mouse osteoblastic cells (2012)
  • Author(s): Nakamura K, Deyama Y, Yoshimura Y, Suzuki K, Morita M
  • Journal Title: Biomedical Research Volume: 33 Issue: 1 Pages: 39-44
  • DOI: 10.2220/biomedres.33.39
  • NAID: 130004470800
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed
• [Journal Article] Effects of bisphosphonates on osteoclastogenesis in RAW264.7 cells (2012)
  • Author(s): Abe K, Yoshimura Y, Deyama Y, et al
  • Journal Title: International Journal of Molecular Medicine Volume: 29 Pages: 1007-1015
  • DOI: 10.3892/ijmm.2012.952
  • Peer Reviewed
• [Journal Article] Effects of bisphosphonates on osteoclastogenesis in RAW 264. 7 cells (2011)
  • Author(s): Abe K, Yoshimura Y, Deyama Y, Kikuiri T, Hasegawa T, Tei K, Shinoda H, Suzuki K, Kitagawa Y
  • Journal Title: Int J Mol Med. Volume: 29 Pages: 1007-1015
  • Peer Reviewed
• [Journal Article] Platinum Nanoparticles Suppress Osteoclastogenesis Through Scavenging of Reactive Oxygen Species Produced in RAW264.7 Cells (2011)
  • Author(s): Nomura M, Yoshimura Y, Kikuiri T, Hasegawa T, Taniguchi Y, Deyama Y, Koshiro K, Sano H, Suzuki K, Inoue N.
  • Journal Title: Journal of Pharmacological Sciences Volume: 117 Issue: 4 Pages: 243-252
  • DOI: 10.1254/jphs.11099FP
  • NAID: 10030453660
  • ISSN: 1347-8613, 1347-8648
  • Peer Reviewed
• [Journal Article] Tannin-fluoride preparation attenuates prostaglandin E2 production by dental pulp cells. (2011)
  • Author(s): Nakamura K, Deyama Y, Yoshimura Y, Hashimoto M, Kaga M, Suzuki K, Yawaka Y.
  • Journal Title: Mol Med Report Volume: 4 Pages: 641-644
  • DOI: 10.3892/mmr.2011.476
  • NAID: 120005946636
  • Peer Reviewed
• [Journal Article] Effect of N-acetylcysteine on rat dental pulp cells cultured on mineral trioxide aggregate (2011)
  • Author(s): Minamikawa H, Yamada M, Deyama Y, Suzuki K, Kaga M, Yawaka Y, Ogawa T
  • Journal Title: J Endod. Volume: 37 Issue: 5 Pages: 637-641
  • DOI: 10.1016/j.joen.2011.02.012
  • Peer Reviewed
• [Journal Article] Effect of the release from mechanical stress on osteoclastogenesis in RAW 264. 7 cells (2011)
  • Author(s): Shibata K, Yoshimura Y, Kikuiri T, Hasegawa T, Taniguchi Y, Deyama Y, Suzuki K, Iida J.
  • Journal Title: Int J Molecular Medicin Volume: 28 Pages: 73-79
  • DOI: 10.3892/ijmm.2011.675
  • Peer Reviewed
• [Journal Article] Tannin-fluoride preparation attenuates prostaglandin E_2 production by dental pulp cells (2011)
  • Author(s): Koichi Nakamura
  • Journal Title: Molecular Medicine Reports Volume: (印刷中,印刷中)
  • Peer Reviewed
• [Journal Article] Amino acid derivative-mediated detoxification and functionalization of dual cure dental restorative material for dental pulp cell mineralization (2010)
  • Author(s): Minamikawa H, Yamada M, Iwasa F, Ueno T, Deyama Y, Suzuki K, Yawaka Y, Ogawa T
  • Journal Title: Biomaterials Volume: 31 Issue: 28 Pages: 7213-7225
  • DOI: 10.1016/j.biomaterials.2010.06.018
  • Peer Reviewed
• [Journal Article] Regulation of human and pig renal Na^+, K^+-ATPase activity by tyrosine phosphorylation of their a1-subunits (2010)
  • Author(s): El-Beialy W, Galal N, Deyama Y, Yoshimura Y, Suzuki K, Tei K, Totsuka Y
  • Journal Title: J Membr Biol. Volume: 233 Issue: 1-3 Pages: 119-126
  • DOI: 10.1007/s00232-010-9231-z
  • Peer Reviewed
• [Journal Article] Effects of Estrogen on PMCA 2 and 4 in Human Fibroblast-like Synovial Cells and Mouse Macrophage-like Cells (2010)
  • Author(s): El-Beialy W, Galal N, Deyama Y, Yoshimura Y, Suzuki K, Tei K, Totsuka Y
  • Journal Title: Endocrine Journal Volume: 57 Issue: 1 Pages: 93-97
  • DOI: 10.1507/endocrj.K09E-247
  • NAID: 130004443571
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed
• [Journal Article] Up-regulation of the G3PDH 'housekeeping' gene by estrogen. (2010)
  • Author(s): Nadia Galal
  • Journal Title: Molecular Medicine Reports Volume: 3 Pages: 111-114
  • Peer Reviewed
• [Journal Article] Effects of estrogen on PMCA 2 and 4 in human fibroblast-like synovial cells and mouse macrophage-like cells. (2010)
  • Author(s): Waleed El-Beialy
  • Journal Title: Endocrine Journal Volume: 57 Pages: 93-97
  • Peer Reviewed
• [Journal Article] Regulation of human and pig renal Na^<+>, K^<+>-ATPase activity by tyrosine phospho-rylation of their α1-subunits. (2010)
  • Author(s): Waleed El-Beialy
  • Journal Title: Journal of Membrane Biology Volume: 233 Pages: 119-126
  • Peer Reviewed
• [Journal Article] Amino acid derivative-mediated detoxification and functionalization of dual cure dental restorative material for dental pulp cell mineralization. (2010)
  • Author(s): Hajime Minamikawa
  • Journal Title: Biomaterials Volume: 31 Pages: 7213-7225
  • Peer Reviewed
• [Journal Article] Up-regulation of the G3PDH housekeeping gene by estrogen (2009)
  • Author(s): Galal N, El-Beialy W, Deyama Y, Yoshimura Y, Tei K, Suzuki K, Totsuka Y.
  • Journal Title: Molecular Medicine reports Volume: 2 Issue: 1 Pages: 111-114
  • DOI: 10.3892/mmr_00000226
  • Peer Reviewed
• [Presentation] Effect of bisphosphonates on osteoclasts and their precursor cells (2012)
  • Author(s): 出山義昭
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2012-03-15
• [Presentation] 二本鎖RNAは骨芽細胞の石灰化を促進する (2011)
  • Author(s): 出山義昭
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-12-16
• [Presentation] Flagellinに反応してマウス骨芽細胞はMCP-1を放出する (2011)
  • Author(s): 出山義昭
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-03-24
• [Presentation] 骨芽細胞におけるMCP-1産生に対するFlagellinの作用 (2010)
  • Author(s): 出山義昭
  • Organizer: 第52回歯科基礎医学会学術大会・総会
  • Place of Presentation: タワーホール船堀(東京都)
  • Year and Date: 2010-09-22
• [Presentation] α1サブユニットのチロシンリン酸化によるNa^+, K^+-ATPase活性の制御 (2010)
  • Author(s): 出山義昭
  • Organizer: 第61回日本薬理学会北部会
  • Place of Presentation: 札幌コンベンションセンター(北海道)
  • Year and Date: 2010-09-10
• [Presentation] α1サブユニットのチロシンリン酸化によるNa^<+>, K^<+>-ATPase活性の制御 (2010)
  • Author(s): 出山義昭
  • Organizer: 第61回日本薬理学会北部会
  • Place of Presentation: 札幌コンベンションセンター(北海道)
  • Year and Date: 2010-09-10
• [Presentation] Fluoride irreversibly inhibits Na, K-ATPase activity with aluminum and divalent cations (2010)
  • Author(s): 出山義昭
  • Organizer: the IADR General Session
  • Place of Presentation: Barcelona(Spain)
  • Year and Date: 2010-07-16
• [Presentation] 関節滑膜細胞のPMCAに対するエストロゲンの作用 (2010)
  • Author(s): 出山義昭
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪市,大阪国際会議場
  • Year and Date: 2010-03-17
• [Presentation] 関節滑膜細胞のPMCAに対するエストロゲンの作用 (2010)
  • Author(s): 出山義昭
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪市, 大阪国際会議場
  • Year and Date: 2010-03-17