Dynamic polarization shifting from M1 to M2 macrophages in reduced osteonecrosis of the jaw-like lesions by cessation of anti-RANKL antibody in mice

• 資料種別: 博士論文
• タイトル: Dynamic polarization shifting from M1 to M2 macrophages in reduced osteonecrosis of the jaw-like lesions by cessation of anti-RANKL antibody in mice
• 巻次・部編番号: 141
• 著者・編者: 玉城, 沙貴
• 著者標目: 玉城, 沙貴
• 出版事項: Elsevier Inc.
• 出版年月日等: 2020-12-02
• 出版年（W3CDTF）: 2020-12-02
• 並列タイトル等: 抗RANKL抗体休薬により作製した顎骨壊死様病変寛解モデルにおけるマクロファージのM１からM２への極性変化
• タイトル（掲載誌）: Bone
• 授与機関名: Nagasaki University (長崎大学)
• 授与年月日: 2020-12-02
• 授与年月日（W3CDTF）: 2020-12-02
• 報告番号: 甲医歯薬第1290号
• 学位: 博士(歯学)
• 博論授与番号: 甲医歯薬第1290号
• 本文の言語コード: eng
• 件名標目: Denosumab; Anti-RANKL antibody; Osteonecrosis of the jaw; Wound healing; Tooth extraction; Macrophage
• 対象利用者: 一般
• 一般注記: Denosumab-related osteonecrosis of the jaw (DRONJ), which mainly occurs in cancer patients receiving anti-receptor activator NF-kappaB ligand (RANKL) antibody, reduces oral health-related quality of life. However, the exact mechanisms of and definitive treatment strategies for DRONJ remain unknown. We hypothesized that cessation of denosumab heals and/or ameliorates DRONJ, since it is a protein-based antibody agent, although stopping denosumab should be avoided in clinical situations. Therefore, the aims of this study were: 1) to create a healing and/or amelioration murine model of DRONJ-like lesions induced by chemotherapy/anti-RANKL antibody (mAb) combination therapy and tooth extraction; and 2) to investigate histopathology and immunopathology in the extraction sockets by comparing the murine model of DRONJ-like lesions with the amelioration/healing model of DRONJ-like lesions. Eight-week-old, female C57B/6J mice received chemotherapeutic drug (cyclophosphamide: CY) and mAb combination therapy (CY/mAb) with tooth extraction. Open wounds were sustained in CY/mAb-treated mice at 2 and 4 weeks post-extraction. Impaired socket healing was diagnosed as CY/mAb-related ONJ-like lesions at 3 weeks post-extraction in this study. Next, mAb was discontinued for 2 and 4 weeks after diagnosis of CY/mAb-related ONJ-like lesions. mAb cessation for 2 weeks induced partial osseous wound healing and significantly improved soft tissue wound healing of the extraction sockets. Anti-angiogenesis and normal lymphangiogenesis with CY/mAb combination therapy was not changed by mAb discontinuation. However, mAb cessation for 2 weeks significantly increased the number of CD38+F4/80+ M1 and CD163+F4/80+ M2 macrophages, which significantly increased the M2/M1 ratio in the connective tissue of extraction sockets. No direct effects of mAb on macrophages were noted both in vivo and in vitro. Therefore, the developed healing and/or amelioration murine model of CY/mAb-related ONJ-like lesions is a useful tool to investigate the histopathology and immunopathology of DRONJ in humans. Dynamic polarization shifting from M1 to M2 macrophages induced by mAb cessation may play an important role in wound healing, rather than angiogenesis and lymphangiogenesis, in DRONJ.; 長崎大学学位論文 学位記番号:博(医歯薬)甲第1290号 学位授与年月日:令和2年12月2日; Author: Saki Tamaki, Shinichiro Kuroshima, Hiroki Hayano, Kazunori Nakajima, Hiroe Kakehashi, Akira Ishisaki, Takashi Sawasea; Citation: Bone, 141, 115560; 2020; identifier:Nagasaki University (長崎大学), 博士(歯学) (2020-12-02); http://hdl.handle.net/10069/40434
• DOI: info:doi/10.1016/j.bone.2020.115560; https://doi.org/info:doi/10.1016/j.bone.2020.115560
• 国立国会図書館永続的識別子: info:ndljp/pid/11644119; https://dl.ndl.go.jp/pid/11644119
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2021-03-07T02:10:05+09:00
• 作成日（W3CDTF）: 2021-01-29
• 記録形式（IMT）: PDF
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 関連情報（URI）: http://hdl.handle.net/10069/40434
• 掲載誌（URI）: http://hdl.handle.net/10069/00040491
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp