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  1. 医歯学総合研究科
  2. 医歯学総合研究科・博士論文

CDC5L promotes early chondrocyte differentiation and proliferation by modulating pre-mRNA splicing of SOX9, COL2A1, and WEE1

http://hdl.handle.net/10232/00031979
http://hdl.handle.net/10232/00031979
2e5eb494-0e7a-4250-9930-485b3f6b21f7
名前 / ファイル ライセンス アクション
Diss_城光寺_豪_ISK640_2021.pdf Diss_城光寺_豪_ISK640_2021 (3.6 MB)
license.icon
Abstract_城光寺_豪_4516810325_2021.pdf Abstract_城光寺_豪_4516810325_2021 (41.0 kB)
Result_Jokoji_Go_isk_640.pdf Result_Jokoji_Go_isk_640 (5.0 MB)
Comments_Jokoji_Go_isk_640.pdf Comments_Jokoji_Go_isk_640 (2.3 MB)
Item type 学位論文 / Thesis or Dissertation(1)
公開日 2022-05-27
タイトル
タイトル CDC5L promotes early chondrocyte differentiation and proliferation by modulating pre-mRNA splicing of SOX9, COL2A1, and WEE1
別言語のタイトル
その他のタイトル 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
著者 城光寺, 豪

× 城光寺, 豪

WEKO 140645

城光寺, 豪

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著者よみ
姓名 ジョウコウジ, ゴウ
別言語の著者
姓名 JOKOJI, Go
言語
言語 eng
キーワード
主題言語 en
主題Scheme Other
主題 ossification of the posterior longitudinal ligament (OPLL)
キーワード
主題言語 en
主題Scheme Other
主題 chondrocyte
キーワード
主題言語 en
主題Scheme Other
主題 cell division cycle 5-like (CDC5L)
キーワード
主題言語 en
主題Scheme Other
主題 Wee1
キーワード
主題言語 en
主題Scheme Other
主題 cell cycle
キーワード
主題言語 en
主題Scheme Other
主題 mRNA splicing
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_db06
資源タイプ doctoral thesis
アクセス権
アクセス権 open access
アクセス権URI http://purl.org/coar/access_right/c_abf2
要約(Abstract)
内容記述タイプ Other
内容記述 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.

Go Jokoji, Shingo Maeda, Kazuki Oishi, Toshiro Ijuin, Masahiro Nakajima, Hiroki Tawaratsumida, Ichiro Kawamura, Hiroyuki Tominaga, Eiji Taketomi, Shiro Ikegawa, and Noboru Taniguchi
CDC5L promotes early chondrocyte differentiation and proliferation by modulating pre-mRNA splicing of SOX9, COL2A1, and WEE1
Journal of Biological Chemistry (2021) 297(2) 100994
https://doi.org/10.1016/j.jbc.2021.100994
作成日
日付 2022-03-04
出版タイプ
出版タイプ VoR
出版タイプResource http://purl.org/coar/version/c_970fb48d4fbd8a85
NDC
主題Scheme NDC
主題 490
ファイル(説明)
内容記述タイプ Other
内容記述 博士論文全文
ファイル(説明)
内容記述タイプ Other
内容記述 博士論文要旨
ファイル(説明)
内容記述タイプ Other
内容記述 最終試験結果の要旨
ファイル(説明)
内容記述タイプ Other
内容記述 論文審査の要旨
公開者・出版者
出版者 American Society for Biochemistry and Molecular Biology
公開者・出版者
出版者 鹿児島大学
公開者よみ
公開者よみ カゴシマ ダイガク
公開者別名
公開者別名 Kagoshima University
備考
備考 【指導教員:谷口昇】
date.appl
【学位申請日】2021-11-04
学位名
学位名 博士(医学)Doctor of Philosophy in Medical Science
学位授与機関
学位授与機関識別子Scheme kakenhi
学位授与機関識別子 17701
学位授与機関名 鹿児島大学
学位授与年月日
学位授与年月日 2022-03-11
学位授与番号
学位授与番号 甲総研第640号
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