{"created":"2023-07-25T08:14:44.333581+00:00","id":15872,"links":{},"metadata":{"_buckets":{"deposit":"68f4145a-c5fd-47fb-8057-1ab0a71f563b"},"_deposit":{"created_by":29,"id":"15872","owners":[29],"pid":{"revision_id":0,"type":"depid","value":"15872"},"status":"published"},"_oai":{"id":"oai:ir.kagoshima-u.ac.jp:00015872","sets":["57:86"]},"author_link":["139482"],"item_5_date_6":{"attribute_name":"作成日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2021-05-11","subitem_date_issued_type":"Collected"}]},"item_5_date_granted_54":{"attribute_name":"学位授与年月日 ","attribute_value_mlt":[{"subitem_dategranted":"2021-05-17"}]},"item_5_degree_grantor_53":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"鹿児島大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"17701","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_5_degree_name_42":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(医学)","subitem_degreename_language":"ja"},{"subitem_degreename":"Doctor of Philosophy in Medical Science","subitem_degreename_language":"en"}]},"item_5_description_17":{"attribute_name":"ファイル（説明）","attribute_value_mlt":[{"subitem_description":"博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_5_description_4":{"attribute_name":"要約(Abstract)","attribute_value_mlt":[{"subitem_description":"Adult bone structural integrity is maintained by remodeling via the coupling of osteoclastic bone resorption and osteoblastic bone formation. Osteocytes or osteoblasts express receptor activator of nuclear factor κ-B ligand (Rankl) or osteoprotegerin (Opg) to promote or inhibit osteoclastogenesis, respectively. Bone morphogenetic protein (BMP) is a potent bone inducer, but its major role in adult bone is to induce osteocytes to upregulate sclerostin (Sost) and increase the Rankl/Opg expression ratio, resulting in promotion of osteoclastogenesis. However, the precise effect of BMP-target gene(s) in osteoblasts on the Rankl/Opg expression ratio remains unclear. In the present study, we identified atonal homolog 8 (Atoh8), which is directly upregulated by the BMPSmad1 axis in osteoblasts. In vivo, Atoh8 was detected in osteoblasts but not osteocytes in adult mice. Although global Atoh8-knockout mice showed only a mild phenotype in the neonate skeleton, the bone volume was decreased and osteoclasts were increased in the adult phase. Atoh8-null marrow stroma cells were more potent than wild-type cells in inducing osteoclastogenesis in marrow cells. Atoh8 loss in osteoblasts increased Runx2 expression and the Rankl/Opg expression ratio, while Runx2 knockdown normalized the Rankl/Opg expression ratio. Moreover, Atoh8 formed a protein complex with Runx2 to inhibit Runx2 transcriptional activity and decrease the Rankl/Opg expression ratio. These results suggest that bone remodeling is regulated elaborately by BMP signaling; while BMP primarily promotes bone resorption, it simultaneously induces Atoh8 to inhibit Runx2 and reduce the Rankl/Opg expression ratio in osteoblasts, suppressing osteoclastogenesis and preventing excessive BMP-mediated bone resorption.\n\nYuhei Yahiro, Shingo Maeda, Masato Morikawa, Daizo Koinuma, Go Jokoji, Toshiro Ijuin, Setsuro Komiya, Ryoichiro Kageyama, Kohei Miyazono and Noboru Taniguchi\nBMP-induced Atoh8 attenuates osteoclastogenesis by suppressing Runx2 transcriptional activity and reducing the Rankl/Opg expression ratio in osteoblasts\nBone Research (2020) 8:32\nhttps://doi.org/10.1038/s41413-020-00106-0","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_5_dissertation_number_55":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲総研第607号"}]},"item_5_publisher_23":{"attribute_name":"公開者・出版者","attribute_value_mlt":[{"subitem_publisher":"nature","subitem_publisher_language":"en"},{"subitem_publisher":"鹿児島大学","subitem_publisher_language":"ja"}]},"item_5_subject_15":{"attribute_name":"NDC","attribute_value_mlt":[{"subitem_subject":"490","subitem_subject_scheme":"NDC"}]},"item_5_text_44":{"attribute_name":"備考","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"【指導教員:谷口昇】"}]},"item_5_text_47":{"attribute_name":"date.appl","attribute_value_mlt":[{"subitem_text_value":"【学位申請日】2021-02-03"}]},"item_5_version_type_14":{"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":"八尋, 雄平","creatorNameLang":"ja"},{"creatorName":"ヤヒロ, ユウヘイ","creatorNameLang":"ja-Kana"},{"creatorName":"Yahiro, Yuhei","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"139482","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-06-01"}],"displaytype":"detail","fileDate":[{"fileDateType":"Collected","fileDateValue":"2021-05-11"}],"filename":"Diss_八尋_雄平_ISK607_2021.pdf","filesize":[{"value":"3.9 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thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"BMP-induced Atoh8 attenuates osteoclastogenesis by suppressing Runx2 transcriptional activity and reducing the Rank1/Opg expression ratio in osteobiasts","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"BMP-induced Atoh8 attenuates osteoclastogenesis by suppressing Runx2 transcriptional activity and reducing the Rank1/Opg expression ratio in osteobiasts","subitem_title_language":"en"},{"subitem_title":"BMP標的遺伝子のAtoh8は骨芽細胞内でのRunx2転写活性やRank1/Opg発現を減弱させることで破骨細胞分化を抑制する","subitem_title_language":"ja"}]},"item_type_id":"5","owner":"29","path":["86"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2021-05-26"},"publish_date":"2021-05-26","publish_status":"0","recid":"15872","relation_version_is_last":true,"title":["BMP-induced Atoh8 attenuates osteoclastogenesis by suppressing Runx2 transcriptional activity and reducing the Rank1/Opg expression ratio in osteobiasts"],"weko_creator_id":"29","weko_shared_id":-1},"updated":"2025-08-28T06:10:47.784444+00:00"}