{"created":"2023-07-25T08:14:54.291315+00:00","id":16093,"links":{},"metadata":{"_buckets":{"deposit":"c2499ffe-6541-4ebe-a45c-4ccb390074f9"},"_deposit":{"created_by":18,"id":"16093","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"16093"},"status":"published"},"_oai":{"id":"oai:ir.kagoshima-u.ac.jp:00016093","sets":["57:86"]},"author_link":["140645"],"item_5_date_6":{"attribute_name":"作成日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2022-03-04","subitem_date_issued_type":"Collected"}]},"item_5_date_granted_54":{"attribute_name":"学位授与年月日 ","attribute_value_mlt":[{"subitem_dategranted":"2022-03-11"}]},"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":"Ossification of the posterior longitudinal ligament (OPLL) of the spine is a common pathological condition that causes intractablemyelopathy and radiculopathy, mainly the result of an endochondral ossification-like process. Our previous genomewide association study identified six susceptibility loci for OPLL, including the cell division cycle 5-like (CDC5L) gene region. Here, we found CDC5L to be expressed in type II collagen-producing chondrocyte-like fibroblasts in human OPLL specimens, as well as in differentiating ATDC5 chondrocytes. Cdc5l siRNA transfection in murine chondrocytes decreased the expression of the early chondrogenic genes Sox9 and Col2a1, diminished the cartilage matrix production, and enhanced the expression of parathyroid-hormone-related protein (a resting chondrocyte marker). We also showed that Cdc5l shRNA suppressed the growth of cultured murine embryonal metatarsal cartilage rudiments and that Cdc5l knockdown suppressed the growth of ATDC5 cells. Fluorescence-activated cell sorting analysis revealed that the G2/Mcell cycle transition was blocked; our data showed that Cdc5l siRNA transfection enhanced expression of Wee1, an inhibitor of the G2/M transition. Cdc5l siRNA also decreased the pre-mRNA splicing efficiency of Sox9 and Col2a1 genes in both ATDC5 cells and primary chondrocytes; conversely, loss of Cdc5l resulted in enhanced splicing of Wee1 pre-mRNA. Finally, an RNA-binding protein immunoprecipitation assay revealed that Cdc5l bound directly to these target gene transcripts.Overall,we conclude thatCdc5l promotes both early chondrogenesis and cartilage growth and may play a role in the etiology of OPLL, at least in part by fine-tuning the pre-mRNA splicing of chondrogenic genes and Wee1, thus initiating the endochondral ossification process.\n\nGo Jokoji, Shingo Maeda, Kazuki Oishi, Toshiro Ijuin, Masahiro Nakajima, Hiroki Tawaratsumida, Ichiro Kawamura, Hiroyuki Tominaga, Eiji Taketomi, Shiro Ikegawa, and Noboru Taniguchi\nCDC5L promotes early chondrocyte differentiation and proliferation by modulating pre-mRNA splicing of SOX9, COL2A1, and WEE1\nJournal of Biological Chemistry (2021) 297(2) 100994\nhttps://doi.org/10.1016/j.jbc.2021.100994","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640号"}]},"item_5_publisher_23":{"attribute_name":"公開者・出版者","attribute_value_mlt":[{"subitem_publisher":"American Society for Biochemistry and Molecular Biology","subitem_publisher_language":"en"},{"subitem_publisher":"鹿児島大学","subitem_publisher_language":"ja"},{"subitem_publisher":"カゴシマ ダイガク","subitem_publisher_language":"ja-Kana"}]},"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_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】2021-11-04"}]},"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":"城光寺, 豪","creatorNameLang":"ja"},{"creatorName":"ジョウコウジ, ゴウ","creatorNameLang":"ja-Kana"},{"creatorName":"Jokoji, Go","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"140645","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":"2022-07-27"}],"displaytype":"detail","filename":"Diss_城光寺_豪_ISK640_2021.pdf","filesize":[{"value":"3.6 MB"}],"format":"application/pdf","licensetype":"license_6","mimetype":"application/pdf","url":{"label":"Diss_城光寺_豪_ISK640_2021","objectType":"fulltext","url":"https://ir.kagoshima-u.ac.jp/record/16093/files/Diss_城光寺_豪_ISK640_2021.pdf"},"version_id":"2de3f233-ab21-4599-bb9d-b212feb66362"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-07-27"}],"displaytype":"detail","filename":"Abstract_城光寺_豪_4516810325_2021.pdf","filesize":[{"value":"41.0 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Abstract_城光寺_豪_4516810325_2021","objectType":"abstract","url":"https://ir.kagoshima-u.ac.jp/record/16093/files/Abstract_城光寺_豪_4516810325_2021.pdf"},"version_id":"7c384221-f233-4b32-9233-144ad68d341e"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-05-27"}],"displaytype":"detail","filename":"Result_Jokoji_Go_isk_640.pdf","filesize":[{"value":"5.0 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Result_Jokoji_Go_isk_640","objectType":"other","url":"https://ir.kagoshima-u.ac.jp/record/16093/files/Result_Jokoji_Go_isk_640.pdf"},"version_id":"8e57816d-add6-41e2-9667-55cd74254578"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-05-27"}],"displaytype":"detail","filename":"Comments_Jokoji_Go_isk_640.pdf","filesize":[{"value":"2.3 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Comments_Jokoji_Go_isk_640","objectType":"other","url":"https://ir.kagoshima-u.ac.jp/record/16093/files/Comments_Jokoji_Go_isk_640.pdf"},"version_id":"2203190a-b095-44c0-a79d-f2083fe40fcb"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"ossification of the posterior longitudinal ligament (OPLL)","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"chondrocyte","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"cell division cycle 5-like (CDC5L)","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Wee1","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"cell cycle","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"mRNA splicing","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":"CDC5L promotes early chondrocyte differentiation and proliferation by modulating pre-mRNA splicing of SOX9, COL2A1, and WEE1","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"CDC5L promotes early chondrocyte differentiation and proliferation by modulating pre-mRNA splicing of SOX9, COL2A1, and WEE1","subitem_title_language":"en"},{"subitem_title":"CDC5LはSOX9, COL2A1, WEE1のpre-mRNAスプライシングを調整し、初期軟骨細胞分化と増殖を促進する","subitem_title_language":"ja"}]},"item_type_id":"5","owner":"18","path":["86"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2022-05-27"},"publish_date":"2022-05-27","publish_status":"0","recid":"16093","relation_version_is_last":true,"title":["CDC5L promotes early chondrocyte differentiation and proliferation by modulating pre-mRNA splicing of SOX9, COL2A1, and WEE1"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2024-01-09T02:06:24.085537+00:00"}