{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363664918987418752.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.3390/cancers12040929"}},{"identifier":{"@type":"URI","@value":"https://www.mdpi.com/2072-6694/12/4/929/pdf"}},{"identifier":{"@type":"PMID","@value":"32283857"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"The Roles of ROS Generation in RANKL-Induced Osteoclastogenesis: Suppressive Effects of Febuxostat"}],"description":[{"type":"abstract","notation":[{"@value":"<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>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1383664918987418753","@type":"Researcher","foaf:name":[{"@value":"Mohannad Ashtar"}],"jpcoar:affiliationName":[{"@value":"Department of Orthodontics and Dentofacial Orthopedics, Tokushima University Graduate School of Oral Sciences, Tokushima 770-8503, Japan"},{"@value":"Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1420282801182330496","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"00829187"},{"@type":"NRID","@value":"1000000829187"},{"@type":"NRID","@value":"9000414841009"},{"@type":"NRID","@value":"9000409175806"},{"@type":"NRID","@value":"9000400189042"},{"@type":"NRID","@value":"9000399534147"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/tenhiro-555"}],"foaf:name":[{"@value":"Hirofumi Tenshin"}],"jpcoar:affiliationName":[{"@value":"Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383664918987418624","@type":"Researcher","foaf:name":[{"@value":"Jumpei Teramachi"}],"jpcoar:affiliationName":[{"@value":"Department of Tissue Regeneration, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, 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Mongolia"}]},{"@id":"https://cir.nii.ac.jp/crid/1420001326226294400","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"90511337"},{"@type":"NRID","@value":"1000090511337"},{"@type":"NRID","@value":"9000399758367"},{"@type":"NRID","@value":"9000412229224"},{"@type":"NRID","@value":"9000331456962"},{"@type":"NRID","@value":"9000415181753"},{"@type":"NRID","@value":"9000414841010"},{"@type":"NRID","@value":"9000391824335"},{"@type":"NRID","@value":"9000410651629"},{"@type":"NRID","@value":"9000400188945"},{"@type":"NRID","@value":"9000409175807"},{"@type":"NRID","@value":"9000400189044"},{"@type":"NRID","@value":"9000014618555"},{"@type":"NRID","@value":"9000413566158"},{"@type":"NRID","@value":"9000403962647"},{"@type":"NRID","@value":"9000002101887"},{"@type":"NRID","@value":"9000262365422"},{"@type":"NRID","@value":"9000414491060"},{"@type":"NRID","@value":"9000399534142"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/sugoiyomasarusan"}],"foaf:name":[{"@value":"Masahiro Hiasa"}],"jpcoar:affiliationName":[{"@value":"Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383664918987418885","@type":"Researcher","foaf:name":[{"@value":"Asuka Oda"}],"jpcoar:affiliationName":[{"@value":"Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383664918987419008","@type":"Researcher","foaf:name":[{"@value":"Kotaro Tanimoto"}],"jpcoar:affiliationName":[{"@value":"Department of Orthodontics and Dentofacial Orthopedics, Tokushima University Graduate School of Oral Sciences, Tokushima 770-8503, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383664918987418754","@type":"Researcher","foaf:name":[{"@value":"So Shimizu"}],"jpcoar:affiliationName":[{"@value":"Department of Orthodontics and Dentofacial Orthopedics, Tokushima University Graduate School of Oral Sciences, Tokushima 770-8503, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383664918987418627","@type":"Researcher","foaf:name":[{"@value":"Yoshiki Higa"}],"jpcoar:affiliationName":[{"@value":"Department of Orthodontics and Dentofacial Orthopedics, Tokushima University Graduate School of Oral Sciences, Tokushima 770-8503, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383664918987419012","@type":"Researcher","foaf:name":[{"@value":"Takeshi Harada"}],"jpcoar:affiliationName":[{"@value":"Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383664918987418757","@type":"Researcher","foaf:name":[{"@value":"Masahiro Oura"}],"jpcoar:affiliationName":[{"@value":"Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383664918987418752","@type":"Researcher","foaf:name":[{"@value":"Kimiko Sogabe"}],"jpcoar:affiliationName":[{"@value":"Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383664918987418760","@type":"Researcher","foaf:name":[{"@value":"Shingen Nakamura"}],"jpcoar:affiliationName":[{"@value":"Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1420282801193059968","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"00618473"},{"@type":"NRID","@value":"1000000618473"},{"@type":"NRID","@value":"9000414835947"},{"@type":"NRID","@value":"9000363355278"},{"@type":"NRID","@value":"9000412234201"},{"@type":"NRID","@value":"9000414841020"},{"@type":"NRID","@value":"9000412316842"},{"@type":"NRID","@value":"9000399534149"}],"foaf:name":[{"@value":"Shiro Fujii"}],"jpcoar:affiliationName":[{"@value":"Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383664918987418625","@type":"Researcher","foaf:name":[{"@value":"Ryohei Sumitani"}],"jpcoar:affiliationName":[{"@value":"Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, 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Kagawa"}],"jpcoar:affiliationName":[{"@value":"Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383664918987418880","@type":"Researcher","foaf:name":[{"@value":"Itsuro Endo"}],"jpcoar:affiliationName":[{"@value":"Department of Chronomedicine, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383664918987419011","@type":"Researcher","foaf:name":[{"@value":"Eiji Tanaka"}],"jpcoar:affiliationName":[{"@value":"Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383664918987418882","@type":"Researcher","foaf:name":[{"@value":"Toshio Matsumoto"}],"jpcoar:affiliationName":[{"@value":"Fujii Memorial Institute of Medical Sciences, Tokushima University,  Tokushima 770-8503, 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myeloma"},{"@id":"https://cir.nii.ac.jp/all?q=ovariectomy","dc:title":"ovariectomy"},{"@id":"https://cir.nii.ac.jp/all?q=RANKL","dc:title":"RANKL"},{"@id":"https://cir.nii.ac.jp/all?q=ROS","dc:title":"ROS"},{"@id":"https://cir.nii.ac.jp/all?q=doxorubicin","dc:title":"doxorubicin"},{"@id":"https://cir.nii.ac.jp/all?q=osteoclastogenesis","dc:title":"osteoclastogenesis"},{"@id":"https://cir.nii.ac.jp/all?q=Article","dc:title":"Article"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040000781917512704","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"16K11504"},{"@type":"JGN","@value":"JP16K11504"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16K11504/"}],"notation":[{"@language":"ja","@value":"TAK-1を標的とした骨破壊抑制と骨形成誘導活性を併せ持った新規抗腫瘍療法の開発"},{"@language":"en","@value":"Development of novel anti-myeloma agents with potent bone anabolic 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