{"created":"2023-05-15T09:58:08.847054+00:00","id":48,"links":{},"metadata":{"_buckets":{"deposit":"057ba516-18dd-4599-928c-57b5bc1fa910"},"_deposit":{"created_by":15,"id":"48","owners":[15],"pid":{"revision_id":0,"type":"depid","value":"48"},"status":"published"},"_oai":{"id":"oai:fdc.repo.nii.ac.jp:00000048","sets":["1:7:8"]},"author_link":[],"item_10006_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2015-03-14"}]},"item_10006_degree_grantor_9":{"attribute_name":"学位授与大学","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"福岡歯科大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"37114"}]}]},"item_10006_degree_name_8":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（歯学）"}]},"item_10006_description_10":{"attribute_name":"学位授与年度","attribute_value_mlt":[{"subitem_description":"2014年度"}]},"item_10006_description_7":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is likely to be caused by continuous imperfection of bone healing after surgical treatments in patients with long-term administration of nitrogen-containing bisphosphonates (NBPs). NBPs inhibit osteoclastic bone resorption by impairing the mevalonic acid sterol pathway in osteoclasts. Thus, we hypothesized that exogenous mevalonic acid metabolites restore the inhibitory effects of NBPs on osteoclastogenesis and bone remodeling. To clarify the effects of mevalonic acid metabolites, especially geranylgeranyl pyrophosphate (GGPP) and geranylgeranyl transferase substrate geranylgeranyl acid (GGOH), we examined the effects of zoledronic acid with or without GGOH or GGPP on osteoclast differentiation, multinucleation, and bone mineral deposition in tooth-extracted sockets. Zoledronic acid decreased the number of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells derived from mouse osteoclast precursors treated with receptor activator of nuclear factor-κB ligand and macrophage colony-stimulating factor. Zoledronic acid simultaneously suppressed not only the expressions of osteoclastic differentiation-related molecules such as TRAP, cathepsin K, calcitonin receptor, and vacuolar H-ATPase but also those of multinucleation-related molecules such as dendrocyte-expressed 7 transmembrane proteins and osteoclast stimulatory transmembrane protein. Treatment with GGOH or GGPP, but not farnesyl acid, restored the zoledronic acid-inhibited number of TRAP-positive multinuclear cells together with the expressions of these molecules. Although intraperitoneal administration of zoledronic acid and lipopolysaccharide into mice appeared to induce BRONJ-like lesions with empty bone lacunae and decreased mineral deposition in tooth-extracted socket, both GGOH and GGPP partially restored the inhibitory effects on zoledronic acid-related mineral deposition. These results suggest the potential of mevalonic acid metabolites as therapeutic agents for BRONJ.","subitem_description_type":"Abstract"}]},"item_10006_dissertation_number_12":{"attribute_name":"報告番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第264号"}]},"item_10006_relation_14":{"attribute_name":"情報源","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"J Dent Res. 2015 Apr;94(4):594-601. doi: 10.1177/0022034514564187. Epub 2014 Dec 22."}]}]},"item_10006_relation_15":{"attribute_name":"関連サイト","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"JDR"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"http://jdr.sagepub.com/content/94/4/594.long","subitem_relation_type_select":"URI"}}]},"item_10006_version_type_18":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Nagaoka, Yoshiyuki"}]},{"creatorNames":[{"creatorName":"Kajiya, Hiroshi"}]},{"creatorNames":[{"creatorName":"Ozeki, Satoru"}]},{"creatorNames":[{"creatorName":"Ikebe, Tetsuro"}]},{"creatorNames":[{"creatorName":"Okabe, Koji"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2015-12-22"}],"displaytype":"detail","filename":"甲第264号_論文(長岡).pdf","filesize":[{"value":"1.1 MB"}],"format":"binary/octet-stream","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"甲第264号_論文(長岡)","objectType":"fulltext","url":"https://fdc.repo.nii.ac.jp/record/48/files/甲第264号_論文(長岡).pdf"},"version_id":"8a41d276-5fb1-4e07-a0f3-d23494dc8bb3"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2015-07-22"}],"displaytype":"detail","filename":"甲第264号_論文内容の要旨(長岡).pdf","filesize":[{"value":"424.9 kB"}],"format":"binary/octet-stream","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"要旨","url":"https://fdc.repo.nii.ac.jp/record/48/files/甲第264号_論文内容の要旨(長岡).pdf"},"version_id":"80929269-8538-4c70-9f57-f4f598fee11f"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2015-07-22"}],"displaytype":"detail","filename":"甲第264号_論文審査結果の要旨(長岡).pdf","filesize":[{"value":"245.4 kB"}],"format":"binary/octet-stream","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"審査結果の要旨","url":"https://fdc.repo.nii.ac.jp/record/48/files/甲第264号_論文審査結果の要旨(長岡).pdf"},"version_id":"d99b815a-c52b-45ec-814b-b2644968518f"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"顎骨壊死"},{"subitem_subject":"破骨細胞"},{"subitem_subject":"骨代謝"},{"subitem_subject":"口腔外科"},{"subitem_subject":"ゲラニルゲラニルピロリン酸"},{"subitem_subject":"細胞融合"},{"subitem_subject":"osteonecrosis","subitem_subject_language":"en"},{"subitem_subject_language":"en"},{"subitem_subject":"osteoclasts","subitem_subject_language":"en"},{"subitem_subject":"oral surgery","subitem_subject_language":"en"},{"subitem_subject":"geranylgeranyl pyrophosphate","subitem_subject_language":"en"},{"subitem_subject":"DC-STAMP","subitem_subject_language":"en"},{"subitem_subject":"Acid Phosphatase","subitem_subject_language":"en"},{"subitem_subject":"Adaptor Proteins, Signal Transducing","subitem_subject_language":"en"},{"subitem_subject":"Animals","subitem_subject_language":"en"},{"subitem_subject":"Bisphosphonate-Associated Osteonecrosis of the Jaw","subitem_subject_language":"en"},{"subitem_subject":"Bone Density Conservation Agents","subitem_subject_language":"en"},{"subitem_subject":"Bone Remodeling","subitem_subject_language":"en"},{"subitem_subject":"Calcification, Physiologic","subitem_subject_language":"en"},{"subitem_subject":"Cathepsin K","subitem_subject_language":"en"},{"subitem_subject":"Cell Differentiation","subitem_subject_language":"en"},{"subitem_subject":"Cells, Cultured","subitem_subject_language":"en"},{"subitem_subject":"Diphosphonates","subitem_subject_language":"en"},{"subitem_subject":"Diterpenes","subitem_subject_language":"en"},{"subitem_subject":"Farnesol","subitem_subject_language":"en"},{"subitem_subject":"Imidazoles","subitem_subject_language":"en"},{"subitem_subject":"Isoenzymes","subitem_subject_language":"en"},{"subitem_subject":"Lipopolysaccharides","subitem_subject_language":"en"},{"subitem_subject":"Macrophages","subitem_subject_language":"en"},{"subitem_subject":"Male","subitem_subject_language":"en"},{"subitem_subject":"Maxilla","subitem_subject_language":"en"},{"subitem_subject":"Membrane Proteins","subitem_subject_language":"en"},{"subitem_subject":"Mevalonic Acid","subitem_subject_language":"en"},{"subitem_subject":"Mice","subitem_subject_language":"en"},{"subitem_subject":"Mice, Inbred C57BL","subitem_subject_language":"en"},{"subitem_subject":"Osteoclasts","subitem_subject_language":"en"},{"subitem_subject":"Polyisoprenyl Phosphates","subitem_subject_language":"en"},{"subitem_subject":"Receptors, Calcitonin","subitem_subject_language":"en"},{"subitem_subject":"Salmonella","subitem_subject_language":"en"},{"subitem_subject":"Tooth Socket","subitem_subject_language":"en"},{"subitem_subject":"Vacuolar Proton-Translocating ATPases","subitem_subject_language":"en"}]},"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":"Mevalonates restore zoledronic acid-induced osteoclastogenesis inhibition.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Mevalonates restore zoledronic acid-induced osteoclastogenesis inhibition.","subitem_title_language":"en"}]},"item_type_id":"10006","owner":"15","path":["8"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2015-07-22"},"publish_date":"2015-07-22","publish_status":"0","recid":"48","relation_version_is_last":true,"title":["Mevalonates restore zoledronic acid-induced osteoclastogenesis inhibition."],"weko_creator_id":"15","weko_shared_id":-1},"updated":"2023-07-11T01:22:19.329522+00:00"}