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

Material type: 博士論文

Author: 城光寺, 豪

Publisher: American Society for Biochemistry and Molecular Biology

Publication date: -

Material Format: Digital

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Name of awarding university/degree: 鹿児島大学,博士(医学),Doctor of Philosophy in Medical Science

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Note (General)：: 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Ossification of the posterior longitudinal ligament (OPLL) of the spine is a common pathological condition that caus...

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Material Type: 博士論文
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
Author/Editor: 城光寺, 豪
Author Heading: 城光寺, 豪ジョウコウジ, ゴウ
Publication, Distribution, etc.: American Society for Biochemistry and Molecular Biology
Alternative Title: CDC5L promotes early chondrocyte differentiation and proliferation by modulating pre-mRNA splicing of SOX9, COL2A1, and WEE1
Degree grantor/type: 鹿児島大学
Date Granted: 2022-03-11
Dissertation Number: 甲総研第640号
Degree Type: 博士(医学)
Doctor of Philosophy in Medical Science
Text Language Code: eng
Subject Heading: ossification of the posterior longitudinal ligament (OPLL)
chondrocyte
cell division cycle 5-like (CDC5L)
Wee1
cell cycle
mRNA splicing
Target Audience: 一般
Note (General): 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
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
Format (IMT): application/pdf
Source: Diss_城光寺_豪_ISK640_2021 （fulltext）
https://ir.kagoshima-u.ac.jp/record/16093/files/Diss_%E5%9F%8E%E5%85%89%E5%AF%BA_%E8%B1%AA_ISK640_2021.pdf
Access Restrictions: インターネット公開
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 鹿児島大学 : 鹿児島大学リポジトリ