• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of treatment strategies for implant induced BRONJ in rats

Research Project

Project/Area Number 18K09664
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57050:Prosthodontics-related
Research InstitutionNagasaki University

Principal Investigator

NAKAJIMA Kazunori  長崎大学, 医歯薬学総合研究科(歯学系), 客員研究員 (40707246)

Co-Investigator(Kenkyū-buntansha) 黒嶋 伸一郎  長崎大学, 医歯薬学総合研究科(歯学系), 准教授 (40443915)
住田 吉慶  長崎大学, 医歯薬学総合研究科(歯学系), 准教授 (50456654)
澤瀬 隆  長崎大学, 医歯薬学総合研究科(歯学系), 教授 (80253681)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsインプラント治療 / 薬剤関連顎骨壊死 / マクロファージ / BRONJ / デンタルインプラント / インプラント / ビスフォスフォネート製剤 / QQ-MNC / 細胞治療 / ステロイド / 幹細胞 / 細胞移植
Outline of Final Research Achievements

The aims of this study were; 1) to create a high-prevalence model of bisphosphonate-related osteonecrosis of the jaw (BRONJ)-like lesion in rats, and; 2) to establish treatment strategy for BRONJ around implants by transplantation of quality and quantity controlled-peripheral blood mononuclear cells (QQ-PBMNCs). A high-prevalence rat model of BRONJ-like lesion around implants were successfully created by bisphosphonate and steroid combination therapy with implant placement. Macrophage polarization was significantly changed in BRONJ-like lesions around implants. Moreover, it was found that systemic transplantation of QQ-PBMNCs significantly healed or ameliorated impaired wound healing around implants. Our data may contribute to the clarification of pathophysiology of and establishment of treatment strategy for BRONJ around dental implants.

Academic Significance and Societal Importance of the Research Achievements

インプラントの治療は日本でも普及しつつあるが,特定の薬を使用する患者では,口の中の傷がいつまでも治らない薬剤関連顎骨壊死という病気が問題となっている.この病気は2003年に発見されたが,現在でもその原因が分かっていない.私たちはその原因を追究すべく動物でこの病気モデルを作成することに成功し,血液から採取した細胞を特殊条件で育てて体内へ戻すことで,この病気が良くなることが分かった.

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (48 results)

All 2021 2020 2019 2018

All Journal Article (12 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 12 results,  Open Access: 6 results) Presentation (36 results) (of which Int'l Joint Research: 10 results,  Invited: 5 results)

  • [Journal Article] Gene expression analysis of fresh extraction wounds prior to onset of bisphosphonate-related osteonecrosis of the jaw-like lesions in mice: A preliminary animal study2021

    • Author(s)
      Kuroshima S, Nakajima K, Sasaki M, Hayano H, Inoue M, Kozutsumi R, Sawase T
    • Journal Title

      Journal of Prosthodontic Research

      Volume: 65 Issue: 4 Pages: 546-553

    • DOI

      10.2186/jpr.JPR_D_20_00027

    • NAID

      130008104554

    • ISSN
      1883-1958, 1883-9207
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Alendronate/dexamethasone combination therapy worsens soft and hard tissue wound healing around implants in rat maxillae2021

    • Author(s)
      Inoue M, Matsumoto C, Nakajima K, Kuroshima S, Sawase T
    • Journal Title

      Bone

      Volume: 148 Pages: 115942-115942

    • DOI

      10.1016/j.bone.2021.115942

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia)2020

    • Author(s)
      Sumita Y, Iwamoto N, Seki M, Yoshida T, Honma R, Iwatake M, Ohba S, Takashi I, Hotokezaka Y, Harada H, Kuroshima S, Nagai K, Asahara T, Atsushi Kawakam I, Asahina I
    • Journal Title

      Medicine (Baltimore)

      Volume: 99 Issue: 26 Pages: e20788-e20788

    • DOI

      10.1097/md.0000000000020788

    • NAID

      120006988135

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Distinct immunopathology in the early stages between different antiresorptive-related osteonecrosis of the jaw-like lesions in mice.2020

    • Author(s)
      Hayano H, Kuroshima S, Sasaki M, Tamki S, Inoue M, Ishisaki A, Sawase T
    • Journal Title

      Bone

      Volume: - Pages: 115308-115308

    • DOI

      10.1016/j.bone.2020.115308

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] A stable protocol for the fabrication of transplantable human oral mucosal epithelial cell sheets for clinical application.2020

    • Author(s)
      Kasai Y, Takagi R, Kobayashi S, Owaki T, Yamaguchi N, Fukuda H, Sakai Y, Sumita Y, Kanai N, Isomoto H, Kanetaka K, Ohki T, Asahina I, Nagai K, Nakao K, Takeda N, Okano T, Eguchi S, Yamato M.
    • Journal Title

      Regen Ther.

      Volume: 14 Pages: 87-94

    • DOI

      10.1016/j.reth.2019.11.007

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Medication-related Osteonecrosis of the Jaw: A Literature Review.2019

    • Author(s)
      Kuroshima S, Sasaki M, Sawase T
    • Journal Title

      J Oral Biosci.

      Volume: 62 Issue: 2 Pages: 99-104

    • DOI

      10.1016/j.job.2019.03.005

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Systemic administration of quality- and quantity-controlled PBMNCs reduces bisphosphonate-related osteonecrosis of the jaw-like lesions in mice2019

    • Author(s)
      Kuroshima S, Nakajima K, Sasaki M, Takashi I, Y Sumita, Asahara T, Asahina I, Sawase T
    • Journal Title

      Stem Cell Res Ther.

      Volume: 10 Issue: 1 Pages: 209-209

    • DOI

      10.1186/s13287-019-1308-8

    • NAID

      120006988442

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Medication-related Osteonecrosis of the Jaw-like Lesions in Rodents: A Comprehensive Systematic Review and Meta-Analysis2019

    • Author(s)
      Kuroshima S, Sasaki M, Murata H, Sawase T.
    • Journal Title

      Gerodontology

      Volume: 36 Issue: 4 Pages: 313-324

    • DOI

      10.1111/ger.12416

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Anti-inflammatory and vasculogenic conditioning of peripheral blood mononuclear cells reinforces their therapeutic potential for radiation-injured salivary glands.2019

    • Author(s)
      I T, Sumita Y, Yoshida T, Honma R, Iwatake M, Raudales JLM, Shizuno T, Kuroshima S, Masuda H, Seki M, Tran SD, Asahara T, Asahina I.
    • Journal Title

      Stem Cell Res Ther.

      Volume: 10 Issue: 1 Pages: 304-304

    • DOI

      10.1186/s13287-019-1414-7

    • NAID

      120006988389

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intra-Bone Marrow Administration of Mesenchymal Stem/Stromal Cells Is a Promising Approach for Treating Osteoporosis.2019

    • Author(s)
      Agata H, Sumita Y, Hidaka T, Iwatake M, Kagami H, Asahina I.
    • Journal Title

      Stem Cells Int

      Volume: 2019 Pages: 4214281-4214281

    • DOI

      10.1155/2019/4214281

    • NAID

      120006988353

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prevalence of bisphosphonate-related osteonecrosis of the jaw-like lesions is increased in a chemotherapeutic dose-dependent manner in mice2018

    • Author(s)
      Kuroshima S, Sasaki M, Nakajima K, Tamaki S, Hayano H, Sawase T
    • Journal Title

      Bone

      Volume: 112 Pages: 177-186

    • DOI

      10.1016/j.bone.2018.05.001

    • NAID

      120006988373

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bone marrow concentrate promotes bone regeneration with a suboptimal-dose of rhBMP-22018

    • Author(s)
      Egashira Kazuhiro、Sumita Yoshinori、Zhong Weijian、I Takashi、Ohba Seigo、Nagai Kazuhiro、Asahina Izumi
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 1 Pages: e0191099-e0191099

    • DOI

      10.1371/journal.pone.0191099

    • NAID

      120006988082

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 高頻度発現型BRONJ様病変の組織・免疫病理学所見と早期遺伝子プロファイル分析2020

    • Author(s)
      黒嶋伸一郎,佐々木宗輝,中島和慶,早野博紀,井上真愛弥,澤瀬 隆
    • Organizer
      公益社団法人日本補綴歯科学会 第129回学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] インプラント周囲に惹起される高頻度発現型BRONJ様病変モデルの作成と病態解析2020

    • Author(s)
      井上真愛弥,松本知生,黒嶋伸一郎,右藤友督,内田悠介,澤瀬 隆
    • Organizer
      公益社団法人日本補綴歯科学会 第129回学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] インプラント周囲に惹起されるビスホスホネート製剤関連顎骨壊死モデルの作成と病態解明研究2020

    • Author(s)
      井上真愛弥,松本知生,黒嶋伸一郎,中島和慶,澤瀬 隆
    • Organizer
      第50回公益社団法人口腔インプラント学会記念学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 骨吸収齲抑制薬関連顎骨壊死の病理学と組織学2020

    • Author(s)
      黒嶋伸一郎,佐々木宗輝,中島和慶,澤瀬 隆
    • Organizer
      第62回歯科基礎歯学会学術大会.日本骨形態計測学会合同シンポジウム【石灰化組織評価の実践とネットワーキング】
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] アレンドロネートとデキサメタゾンがデンタルインプラント周囲硬軟組織に与える影響2020

    • Author(s)
      井上真愛弥,松本知生,黒嶋伸一郎,右藤友督,内田悠介,稲葉菜緒,澤瀬 隆
    • Organizer
      第38回日本骨代謝学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 高頻度発現型BRONJマウスモデルを用いた早期における遺伝子パターン解析2020

    • Author(s)
      黒嶋伸一郎,早野博紀,佐々木宗輝,中島和慶,澤瀬 隆
    • Organizer
      第38回日本骨代謝学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Relationship between gene profiles and histopathology/immunopathology in high-prevalence BRONJ-like lesions in mice2020

    • Author(s)
      Kuroshima S, Sasaki M, Hayano H, Kozutsumi R, Inoue M, Sawase T
    • Organizer
      30th Annual Congress of the European College of Gerodontology
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Histopathology/immunopathology in high-prevalence bisphosphonate-related osteonecrosis of the jaw around implants in rat maxillae2020

    • Author(s)
      Inoue M, Matsumoto C, Nakajima K, Hayano H, Kozutsumi R, Kuroshima S, Sawase T
    • Organizer
      30th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting Virtual
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Gene expression profiling and histopathology/immunopathology in high-prevalence bisphosphonate-related osteonecrosis of the jaw in mice2020

    • Author(s)
      Kuroshima S, Sasaki M, Nakajima K, Hayano H, Inoue M, Kozutsumi R, Sawase T
    • Organizer
      30th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting Virtual
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] BRONJを緩解するSVF細胞とQQMNC細胞移植は抜歯窩治癒に異なった影響を与える2019

    • Author(s)
      黒嶋伸一郎,佐々木宗輝,玉城沙貴,早野博紀,澤瀬 隆
    • Organizer
      公益社団法人日本補綴歯科学会 第128回学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 抗RANKL抗体製剤誘発性顎骨壊死は薬剤の休薬によりその病態を治癒させる2019

    • Author(s)
      玉城沙貴,黒嶋伸一郎,早野博紀,井上真愛弥,澤瀬 隆
    • Organizer
      公益社団法人日本補綴歯科学会 第128回学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Effect of phosphorus on osteocyte function and aging2019

    • Author(s)
      Sasaki M, Kuroshima S, Sawase T
    • Organizer
      Secretariat of the 7th Seoul Symposium on Bone Health (SSBH 2019) & the 31th Annual Meeting of the Korean Society for Bone and Mineral Research(KSBMR)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effects of antiresorptives/chemotherapeutic combination therapy on tooth extraction socket healing2019

    • Author(s)
      Hayano H, Kuroshima S, Tamaki S, Inoue M, Sawase T
    • Organizer
      97th General session & Exhibition of the IADR
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Transplantation of SVF cells and QQ-MNCs reduces BRONJ-like lesions through distinct healing processes in mice2019

    • Author(s)
      Kuroshima S, Sasaki M, Hayano H, Tamaki S, Inoue M, Sawase T
    • Organizer
      97th General session & Exhibition of the IADR
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 抗RANKL抗体製剤誘発性高頻度発現型マウス顎骨壊死様病変モデルの開発2019

    • Author(s)
      黒嶋伸一郎,早野博紀,右藤友督,玉城沙貴,小堤涼平,澤瀬 隆
    • Organizer
      第5回日本骨免疫学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 高機能化末梢血由来単核細胞移植が高頻度発現型マウスBRONJ様病変モデルに与える影響2019

    • Author(s)
      黒嶋伸一郎,佐々木宗輝,早野博紀,玉城沙貴,澤瀬 隆
    • Organizer
      第39回日本骨形態計測学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 骨吸収抑制薬と抗癌剤の併用投与がマウス抜歯窩治癒に与える影響2019

    • Author(s)
      早野博紀,黒嶋伸一郎,玉城沙貴,澤瀬 隆
    • Organizer
      第39回日本骨形態計測学会
    • Related Report
      2019 Research-status Report
  • [Presentation] デノスマブ関連顎骨壊死の寛解には脈管新生よりも組織修復性マクロファージの集積が重要な役割を果たす2019

    • Author(s)
      玉城沙貴,黒嶋伸一郎,早野博紀,井上真愛弥,佐々木宗輝,澤瀬 隆
    • Organizer
      第49回公益社団法人日本口腔インプラント学会学術大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 抗RANKL抗体製剤の休止が高頻度発現型マウス顎骨壊死様病変に与える影響2019

    • Author(s)
      黒嶋伸一郎,玉城沙貴,早野博紀,井上真愛弥,澤瀬 隆
    • Organizer
      第37回日本骨代謝学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 免疫病理組織所見が異なるビスフォスフォネート製剤と抗RANKL抗体誘発性顎骨壊死様病変2019

    • Author(s)
      早野博紀,黒嶋伸一郎,玉城沙貴,井上真愛弥,澤瀬 隆
    • Organizer
      第37回日本骨代謝学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Effects of cell transplantation on BRONJ-like lesions are quite different between SVF and QQ-MNCs2019

    • Author(s)
      Kuroshima S, Sasaki M, Nakajima K, Sawase T
    • Organizer
      29th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Upregulated macrophage distribution in reduced osteonecrosis of the jaw-like lesions by the discontinuation of anti-RANKL antibody in mice2019

    • Author(s)
      Tamaki S, Kuroshima S, Hayano H, Inoue M, Nakajima K, Sasaki M, Sawase T
    • Organizer
      29th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] シンポジウム1.適切な介入を支える基礎研究・臨床研究 ―薬剤関連顎骨壊死に関する基礎・トランスレーショナル・臨床研究の最前線―2019

    • Author(s)
      黒嶋伸一郎
    • Organizer
      特定非営利活動法人 日本がん口腔支持療法学会第5回学術大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 薬剤関連顎骨壊死の病因解明と治療法開発に向けて.2018

    • Author(s)
      黒嶋伸一郎
    • Organizer
      第17回松本ボーンフォーラム
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 補綴治療に求められる骨質を科学する.「骨質を基盤とした補綴歯科治療戦略は必要か」2018

    • Author(s)
      黒嶋伸一郎
    • Organizer
      公益社団法人日本補綴歯科学会 第127回学術大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 骨吸収抑制薬がマウスの抜歯窩治癒に与える影響2018

    • Author(s)
      早野博紀,黒嶋伸一郎,佐々木宗輝,玉城沙貴,澤瀬 隆
    • Organizer
      公益社団法人日本補綴歯科学会 第127回学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 抗癌剤の濃度依存性に増大するビスフォスフォネート製剤関連顎骨壊死の有病率2018

    • Author(s)
      黒嶋伸一郎,佐々木宗輝,早野博紀,玉城沙貴,澤瀬 隆
    • Organizer
      第38回日本骨形態計測学会
    • Related Report
      2018 Research-status Report
  • [Presentation] BP製剤と抗RANKL抗体製剤がマウス抜歯窩治癒に与える影響2018

    • Author(s)
      早野博紀,黒嶋伸一郎,玉城沙貴,澤瀬 隆
    • Organizer
      第38回日本骨形態計測学会
    • Related Report
      2018 Research-status Report
  • [Presentation] QQ-MNC移植は高頻度発現型マウスBRONJ様病態を緩解させる2018

    • Author(s)
      黒嶋伸一郎,佐々木宗輝,住田吉慶,朝比奈 泉,澤瀬 隆
    • Organizer
      第4回日本骨免疫学会
    • Related Report
      2018 Research-status Report
  • [Presentation] ビスフォスフォネート製剤関連顎骨壊死の有病率は抗癌剤の濃度依存性に増大する2018

    • Author(s)
      黒嶋伸一郎,佐々木宗輝,早野博紀,玉城沙貴,澤瀬 隆
    • Organizer
      第36回日本骨代謝学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 骨吸収抑制薬と抗癌剤の併用投与がマウス抜歯窩治癒に与える影響2018

    • Author(s)
      早野博紀,黒嶋伸一郎,玉城沙貴,稲葉菜緒,澤瀬 隆
    • Organizer
      第36回日本骨代謝学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 口腔インプラント治療と研究をつなぐ.「骨質を基軸とした新規インプラントの開発とインプラント-薬剤関連顎骨壊死の病態解明に向けた取り組み」2018

    • Author(s)
      黒嶋伸一郎
    • Organizer
      平成30年度公益社団法人日本補綴歯科学会九州支部学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Bisphosphonate-related osteonecrosis of the jaw-like lesions in prevalently induced in a chemotherapeutic dose-dependent manner in mice2018

    • Author(s)
      Kuroshima S, Sasaki M, Hayano H, Tamaki S, Sawase T
    • Organizer
      28th Annual scientific meeting of the Australian and New Zealand Bone and Mineral Society
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] ビスフォスフォネート製剤とデノスマブ誘発性顎骨壊死の病因・病態は脈管形成依存性に異なる2018

    • Author(s)
      早野博紀,黒嶋伸一郎,佐々木宗輝,玉城沙貴,澤瀬 隆
    • Organizer
      第48回公益社団法人日本口腔インプラント学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 破骨細胞分化因子に対する中和抗体の休薬が抜歯窩治癒と長管骨微小環境に与える影響2018

    • Author(s)
      玉城沙貴,黒嶋伸一郎,早野博紀,佐々木宗輝,井上真愛弥,澤瀬 隆
    • Organizer
      公益社団法人口腔インプラント学会第36回九州支部学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Medication-related Osteonecrosis of the Jaw -Pathology, Pathogenesis and Treatment Strategies-2018

    • Author(s)
      Kuroshima S
    • Organizer
      60th Anniversary of the KAP & 6th Biennial Joint Congress of KAP-CPS-JPS
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi