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

• Material Type: 博士論文
• ISSN: 2072-6694
• Title: The Roles of ROS Generation in RANKL-Induced Osteoclastogenesis : Suppressive Effects of Febuxostat
• Volume: 12 4
• 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
• Degree grantor/type: 徳島大学
• Date Granted: 2020-12-10
• Date Granted (W3CDTF): 2020-12-10
• Dissertation Number: 甲第3467号
• Degree Type: 博士（歯学）
• Conferring No. (Dissertation): 甲第3467号
• 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.
• DOI: info:doi/10.3390/cancers12040929; https://doi.org/info:doi/10.3390/cancers12040929
• Persistent ID (NDL): info:ndljp/pid/11671790; https://dl.ndl.go.jp/pid/11671790
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 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
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2021-05-16T23:51:55+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/115041
• Data Provider (Database): 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