The Roles of ROS Generation in RANKL-Induced Osteoclastogenesis : Suppressive Effects of Febuxostat

• 資料種別: 博士論文
• ISSN: 2072-6694
• タイトル: The Roles of ROS Generation in RANKL-Induced Osteoclastogenesis : Suppressive Effects of Febuxostat
• 巻次・部編番号: 12 4
• 著者・編者: Ashtar, Mohannad; Tenshin, Hirofumi; Teramachi, Jumpei; Bat-Erdene, Ariunzaya; Hiasa, Masahiro; Oda, Asuka; Tanimoto, Kotaro; Shimizu, So; Higa, Yoshiki; Harada, Takeshi; Oura, Masahiro; Sogabe, Kimiko; Nakamura, Shingen; Fujii, Shiro; Sumitani, Ryohei; Miki, Hirokazu; Udaka, Kengo; Takahashi, Mamiko; Kagawa, Kumiko; Endo, Itsuro; Tanaka, Eiji; Matsumoto, Toshio; Abe, Masahiro
• 著者標目: Ashtar, Mohannad; Tenshin, Hirofumi; Teramachi, Jumpei; Bat-Erdene, Ariunzaya; Hiasa, Masahiro; Oda, Asuka; Tanimoto, Kotaro; Shimizu, So; Higa, Yoshiki; Harada, Takeshi; Oura, Masahiro; Sogabe, Kimiko; Nakamura, Shingen; Fujii, Shiro; Sumitani, Ryohei; Miki, Hirokazu; Udaka, Kengo; Takahashi, Mamiko; Kagawa, Kumiko; Endo, Itsuro; Tanaka, Eiji; Matsumoto, Toshio; Abe, Masahiro
• 出版事項: MDPI
• 出版年月日等: 2020-04-09
• 出版年（W3CDTF）: 2020-04-09
• 並列タイトル等: RANKLが誘導する破骨細胞分化におけるROSの役割と、Febuxostatによる破骨細胞分化抑制効果
• タイトル（掲載誌）: Cancers
• 授与機関名: 徳島大学
• 授与年月日: 2020-12-10
• 授与年月日（W3CDTF）: 2020-12-10
• 報告番号: 甲第3467号
• 学位: 博士（歯学）
• 博論授与番号: 甲第3467号
• 本文の言語コード: eng
• 件名標目: RANKL; ROS; doxorubicin; multiple myeloma; osteoclastogenesis; ovariectomy
• 対象利用者: 一般
• 一般注記: Receptor activator of NF-κB ligand (RANKL), a critical mediator of osteoclastogenesis, is upregulated in multiple myeloma (MM). The xanthine oxidase inhibitor febuxostat, clinically used for prevention of tumor lysis syndrome, has been demonstrated to effectively inhibit not only the generation of uric acid but also the formation of reactive oxygen species (ROS). ROS has been demonstrated to mediate RANKL-mediated osteoclastogenesis. In the present study, we therefore explored the role of cancer-treatment-induced ROS in RANKL-mediated osteoclastogenesis and the suppressive effects of febuxostat on ROS generation and osteoclastogenesis. RANKL dose-dependently induced ROS production in RAW264.7 preosteoclastic cells; however, febuxostat inhibited the RANKL-induced ROS production and osteoclast (OC) formation. Interestingly, doxorubicin (Dox) further enhanced RANKL-induced osteoclastogenesis through upregulation of ROS production, which was mostly abolished by addition of febuxostat. Febuxostat also inhibited osteoclastogenesis enhanced in cocultures of bone marrow cells with MM cells. Importantly, febuxostat rather suppressed MM cell viability and did not compromise Dox’s anti-MM activity. In addition, febuxostat was able to alleviate pathological osteoclastic activity and bone loss in ovariectomized mice. Collectively, these results suggest that excessive ROS production by aberrant RANKL overexpression and/or anticancer treatment disadvantageously impacts bone, and that febuxostat can prevent the ROS-mediated osteoclastic bone damage.
• DOI: info:doi/10.3390/cancers12040929; https://doi.org/info:doi/10.3390/cancers12040929
• 国立国会図書館永続的識別子: info:ndljp/pid/11671790; https://dl.ndl.go.jp/pid/11671790
• 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）: 2021-05-16T23:51:55+09:00
• 記録形式（IMT）: application/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
• 掲載誌（URI）: http://repo.lib.tokushima-u.ac.jp/115041
• 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