アクセス数 : ?
ダウンロード数 : ?
ID 115041
著者
Ashtar, Mohannad Tokushima University
Bat-Erdene, Ariunzaya Mongolian National University of Medical Sciences
Oda, Asuka Tokushima University
谷本, 幸多朗 Tokushima University
清水, 宗 Tokushima University
Higa, Yoshiki Tokushima University
曽我部, 公子 Tokushima University
住谷, 龍平 Tokushima University
Udaka, Kengo Tokushima University
Takahashi, Mamiko Tokushima University
キーワード
multiple myeloma
osteoclastogenesis
RANKL
ROS
doxorubicin
ovariectomy
資料タイプ
学術雑誌論文
抄録
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.
掲載誌名
Cancers
ISSN
20726694
出版者
MDPI
12
4
開始ページ
929
発行日
2020-04-09
権利情報
© 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/).
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
歯学系
病院
医学系
先端酵素学研究所