The Roles of ROS Generation in RANKL-Induced Osteoclastogenesis: Suppressive Effects of Febuxostat
-
- Mohannad Ashtar
- Department of Orthodontics and Dentofacial Orthopedics, Tokushima University Graduate School of Oral Sciences, Tokushima 770-8503, Japan
-
- Hirofumi Tenshin
- Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan
-
- Jumpei Teramachi
- Department of Tissue Regeneration, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan
-
- Ariunzaya Bat-Erdene
- Department of Immunology, School of Bio-Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia
-
- Masahiro Hiasa
- Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan
-
- Asuka Oda
- Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan
-
- Kotaro Tanimoto
- Department of Orthodontics and Dentofacial Orthopedics, Tokushima University Graduate School of Oral Sciences, Tokushima 770-8503, Japan
-
- So Shimizu
- Department of Orthodontics and Dentofacial Orthopedics, Tokushima University Graduate School of Oral Sciences, Tokushima 770-8503, Japan
-
- Yoshiki Higa
- Department of Orthodontics and Dentofacial Orthopedics, Tokushima University Graduate School of Oral Sciences, Tokushima 770-8503, Japan
-
- Takeshi Harada
- Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan
-
- Masahiro Oura
- Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan
-
- Kimiko Sogabe
- Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan
-
- Shingen Nakamura
- Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan
-
- Shiro Fujii
- Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan
-
- Ryohei Sumitani
- Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan
-
- Hirokazu Miki
- Division of Transfusion Medicine and Cell Therapy, Tokushima University Hospital, Tokushima 770-8503, Japan
-
- Kengo Udaka
- Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan
-
- Mamiko Takahashi
- Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan
-
- Kumiko Kagawa
- Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan
-
- Itsuro Endo
- Department of Chronomedicine, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan
-
- Eiji Tanaka
- Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan
-
- Toshio Matsumoto
- Fujii Memorial Institute of Medical Sciences, Tokushima University, Tokushima 770-8503, Japan
-
- Masahiro Abe
- Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan
書誌事項
- 公開日
- 2020-04-09
- 資源種別
- journal article
- 権利情報
-
- https://creativecommons.org/licenses/by/4.0/
- DOI
-
- 10.3390/cancers12040929
- 公開者
- MDPI AG
説明
<jats:p>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.</jats:p>
収録刊行物
-
- Cancers
-
Cancers 12 (4), 929-, 2020-04-09
MDPI AG
