{"created":"2024-10-28T05:49:11.789997+00:00","id":2004899,"links":{},"metadata":{"_buckets":{"deposit":"9e4e9b4c-5a64-40eb-9e73-f70262448b2d"},"_deposit":{"created_by":7,"id":"2004899","owners":[7],"pid":{"revision_id":0,"type":"depid","value":"2004899"},"status":"published"},"_oai":{"id":"oai:tokushima-u.repo.nii.ac.jp:02004899","sets":["1713853213384:1713853296295:1716267877313:1716268556148"]},"author_link":["723","384","326","458","876","450","919","528","580","833","518","1224","230","323","1591","1634"],"control_number":"2004899","item_10001_alternative_title_1":{"attribute_name":"タイトル別表記","attribute_value_mlt":[{"subitem_alternative_title":"TAK1阻害はTRAILの抗骨髄腫作用を増強するともに骨吸収促進活性を抑制活性に変換する","subitem_alternative_title_language":"ja"},{"subitem_alternative_title":"MODULATION OF TRAIL ACTION BY TAK1 INHIBITION","subitem_alternative_title_language":"en"}]},"item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2017-10-26","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"24","bibliographicPageEnd":"2137","bibliographicPageStart":"2124","bibliographicVolumeNumber":"1","bibliographic_titles":[{"bibliographic_title":"Blood Advances","bibliographic_titleLang":"en"}]}]},"item_10001_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) agonists induce tumor-specific apoptosis indicating that they may be an attractive therapeutic strategy against cancers, including multiple myeloma (MM). Osteoclastogenesis is highly induced in MM, which in turn enhances MM growth, thereby forming a vicious cycle between MM tumor expansion and bone destruction. However, the effects of TRAIL on MM-enhanced osteoclastogenesis remain largely unknown. Here, we show that TRAIL induced apoptosis in MM cells, but not in osteoclasts (OCs), and that it rather facilitated receptor activator of NF-kB ligand–induced osteoclastogenesis along with upregulation of cellular FLICE inhibitory protein (c-FLIP). TRAIL did not induce death-inducing signaling complex formation in OCs, but formed secondary complex (complex II) with the phosphorylation of transforming growth factor β–activated kinase-1 (TAK1), and thus activated NF-kB signaling. c-FLIP knockdown abolished complex II formation, thus permitting TRAIL induction of OC cell death. The TAK1 inhibitor LLZ1640-2 abrogated the TRAIL-induced c-FLIP upregulation and NF-kB activation, and triggered TRAIL-induced caspase-8 activation and cell death in OCs. Interestingly, the TRAIL-induced caspase-8 activation caused enzymatic degradation of the transcription factor Sp1 to noticeably reduce c-FLIP expression, which further sensitized OCs to TRAIL-induced apoptosis. Furthermore, the TAK1 inhibition induced antiosteoclastogenic activity by TRAIL even in cocultures with MM cells while potentiating TRAIL’s anti-MM effects. These results demonstrated that osteoclastic lineage cells use TRAIL for their differentiation and activation through tilting caspase-8–dependent apoptosis toward NF-kB activation, and that TAK1 inhibition subverts TRAIL-mediated NF-kB activation to resume TRAIL-induced apoptosis in OCs while further enhancing MM cell death in combination with TRAIL.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"The American Society of Hematology","subitem_publisher_language":"en"}]},"item_10001_source_id_9":{"attribute_name":"収録物ID","attribute_value_mlt":[{"subitem_source_identifier":"24739529","subitem_source_identifier_type":"ISSN"},{"subitem_source_identifier":"24739537","subitem_source_identifier_type":"ISSN"}]},"item_10001_version_type_20":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_be7fb7dd8ff6fe43","subitem_version_type":"NA"}]},"item_1714461018643":{"attribute_name":"報告番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第3175号"}]},"item_1714461102074":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（歯学）","subitem_degreename_language":"ja"}]},"item_1714461118377":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2018-03-23"}]},"item_1714461137393":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"徳島大学"}]}]},"item_1715043197608":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access"}]},"item_1718868208704":{"attribute_name":"備考","attribute_value_mlt":[{"subitem_textarea_language":"ja","subitem_textarea_value":"内容要旨・審査要旨・論文本文の公開\n本論文は, 著者Hirofumi Tenshin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。\n学位授与者所属 : 徳島大学大学院口腔科学教育部（口腔科学専攻）"}]},"item_1718868303842":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"甲口第432号"}]},"item_1722929371688":{"attribute_name":"出版社版DOI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_language":"ja","subitem_relation_name_text":"10.1182/bloodadvances.2017008813"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1182/bloodadvances.2017008813","subitem_relation_type_select":"DOI"}}]},"item_1723180141928":{"attribute_name":"EID","attribute_value_mlt":[{"subitem_identifier_type":"URI","subitem_identifier_uri":"336276"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"天眞, 寛文","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"723","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"寺町, 順平","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"384","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"オダ, アスカ","creatorNameLang":"ja"},{"creatorName":"オダ, アスカ","creatorNameLang":"ja-Kana"},{"creatorName":"Oda, Asuka","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"天知, 良太","creatorNameLang":"ja"},{"creatorName":"アマチ, リョウタ","creatorNameLang":"ja-Kana"},{"creatorName":"Amachi, Ryota","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"日浅, 雅博","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"326","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Bat-Erdene, Ariunzaya","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"渡邉, 佳一郎","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"458","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"イワサ, マサミ","creatorNameLang":"ja"},{"creatorName":"イワサ, マサミ","creatorNameLang":"ja-Kana"},{"creatorName":"Iwasa, Masami","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"原田, 武志","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"876","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"藤井, 志朗","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"450","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"賀川, 久美子","creatorNameLang":"ja"},{"creatorName":"カガワ, クミコ","creatorNameLang":"ja-Kana"},{"creatorName":"Kagawa, Kumiko","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"曽我部, 公子","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"919","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"中村, 信元","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"528","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"三木, 浩和","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"580","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"倉橋, 清衛","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"833","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"吉田, 守美子","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"518","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"粟飯原, 賢一","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"1224","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"遠藤, 逸朗","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"230","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"田中, 栄二","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"323","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"松本, 俊夫","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"1591","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"安倍, 正博","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"1634","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2018-06-11"}],"displaytype":"detail","filename":"k3175_abstract.pdf","filesize":[{"value":"80.2 KB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"objectType":"abstract","url":"https://tokushima-u.repo.nii.ac.jp/record/2004899/files/k3175_abstract.pdf"},"version_id":"4eb3ccbe-2b3a-426f-aed4-89cbdb145785"},{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2018-06-11"}],"displaytype":"detail","filename":"k3175_review.pdf","filesize":[{"value":"338 KB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"objectType":"other","url":"https://tokushima-u.repo.nii.ac.jp/record/2004899/files/k3175_review.pdf"},"version_id":"76e6918a-c1dd-483b-b469-6185ad4dc314"},{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2018-06-11"}],"displaytype":"detail","filename":"k3175_fulltext.pdf","filesize":[{"value":"2.78 MB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"objectType":"fulltext","url":"https://tokushima-u.repo.nii.ac.jp/record/2004899/files/k3175_fulltext.pdf"},"version_id":"848573e6-2772-4463-bd86-94c8d8cf7fc0"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Immunology","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Multiple myeloma","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Osteoclastgenesis","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"TRAIL","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"TAK1","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"TAK1 inhibition subverts the osteoclastogenic action of TRAIL while potentiating its antimyeloma effects","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"TAK1 inhibition subverts the osteoclastogenic action of TRAIL while potentiating its antimyeloma effects","subitem_title_language":"en"}]},"item_type_id":"40001","owner":"7","path":["1716268556148"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2018-06-11"},"publish_date":"2018-06-11","publish_status":"0","recid":"2004899","relation_version_is_last":true,"title":["TAK1 inhibition subverts the osteoclastogenic action of TRAIL while potentiating its antimyeloma effects"],"weko_creator_id":"7","weko_shared_id":-1},"updated":"2024-12-18T06:08:51.165911+00:00"}