ID | 115041 |
Title Alternative | 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
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Author |
Ashtar, Mohannad
Tokushima University
Teramachi, Jumpei
Tokushima University
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Bat-Erdene, Ariunzaya
Mongolian National University of Medical Sciences
Hiasa, Masahiro
Tokushima University
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Oda, Asuka
Tokushima University
Tanimoto, Kotaro
Tokushima University
Higa, Yoshiki
Tokushima University
Nakamura, Shingen
Tokushima University
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Fujii, Shiro
Tokushima University
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Miki, Hirokazu
Tokushima University
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Udaka, Kengo
Tokushima University
Takahashi, Mamiko
Tokushima University
Endo, Itsuro
Tokushima University
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Tanaka, Eiji
Tokushima University
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Matsumoto, Toshio
Tokushima University
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Abe, Masahiro
Tokushima University
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Keywords | RANKL
ROS
doxorubicin
multiple myeloma
osteoclastogenesis
ovariectomy
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Content Type |
Thesis or Dissertation
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Description | 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.
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Journal Title |
Cancers
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ISSN | 20726694
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Publisher | MDPI
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Volume | 12
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Issue | 4
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Start Page | 929
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Published Date | 2020-04-09
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Remark | 内容要旨・審査要旨・論文本文の公開
本論文は,著者Mohannad Ashtarの学位論文として提出され,学位審査・授与の対象となっている。 |
Rights | © 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/).
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EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
ETD
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MEXT report number | 甲第3467号
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Diploma Number | 甲口第466号
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Granted Date | 2020-12-10
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Degree Name |
Doctor of Dental Science
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Grantor |
Tokushima University
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departments |
Oral Sciences
University Hospital
Medical Sciences
Institute of Advanced Medical Sciences
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