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

• Material Type: 博士論文
• Title: The Roles of ROS Generation in RANKL-Induced Osteoclastogenesis : Suppressive Effects of Febuxostat
• Author/Editor: 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
• Author Heading: 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
• Publication, Distribution, etc.: MDPI
• Publication Date: 2020-04-09
• Publication Date (W3CDTF): 2020-04-09
• Alternative Title: 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
• Periodical title: Cancers
• No. or year of volume/issue: 12 4
• Volume: 12
• Issue: 4
• Pages: 929-
• ISSN (Periodical Title): ISSN : 2072-6694
• Degree grantor/type: 徳島大学
• Date Granted: 2020-12-10
• Dissertation Number: 甲第3467号
• Degree Type: 博士（歯学）
• Text Language Code: eng
• Subject Heading: RANKL; ROS; doxorubicin; multiple myeloma; osteoclastogenesis; ovariectomy
• Target Audience: 一般
• Note (General): 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
• Related Material (DOI): 10.3390/cancers12040929
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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http://repo.lib.tokushima-u.ac.jp/files/public/11/115041/20201221141952700552/k3467_abstract.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/115041/20201221141953287925/k3467_review.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/115041/20201221141953635189/k3467_fulltext.pdf fulltext