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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
http://hdl.handle.net/10232/00031760
http://hdl.handle.net/10232/000317605b245824-c897-4509-9655-d72374f463ea
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Diss_八尋_雄平_ISK607_2021 (3.9 MB)
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Abstract_八尋_雄平_4513810232_2020 (103.1 kB)
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Result_Yahiro_Yuhei_isk_607 (890.4 kB)
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Commets_Yahiro_Yuhei_isk_607 (480.3 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-05-26 | |||||
| タイトル | ||||||
| タイトル | BMP-induced Atoh8 attenuates osteoclastogenesis by suppressing Runx2 transcriptional activity and reducing the Rank1/Opg expression ratio in osteobiasts | |||||
| タイトル言語 | en | |||||
| タイトル | ||||||
| タイトル | 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 | |||||
| タイトル言語 | ja | |||||
| 著者 |
八尋, 雄平
× 八尋, 雄平 |
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| 言語 | ||||||
| 言語 | eng | |||||
| 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 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 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. Yuhei Yahiro, Shingo Maeda, Masato Morikawa, Daizo Koinuma, Go Jokoji, Toshiro Ijuin, Setsuro Komiya, Ryoichiro Kageyama, Kohei Miyazono and Noboru Taniguchi BMP-induced Atoh8 attenuates osteoclastogenesis by suppressing Runx2 transcriptional activity and reducing the Rankl/Opg expression ratio in osteoblasts Bone Research (2020) 8:32 https://doi.org/10.1038/s41413-020-00106-0 |
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| 内容記述言語 | en | |||||
| 作成日 | ||||||
| 日付 | 2021-05-11 | |||||
| 日付タイプ | Collected | |||||
| 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 | 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 | |||||
| 公開者・出版者 | ||||||
| 出版者 | nature | |||||
| 出版者言語 | en | |||||
| 公開者・出版者 | ||||||
| 出版者 | 鹿児島大学 | |||||
| 出版者言語 | ja | |||||
| 備考 | ||||||
| 備考言語 | ja | |||||
| 備考 | 【指導教員:谷口昇】 | |||||
| date.appl | ||||||
| appl | 【学位申請日】2021-02-03 | |||||
| 学位名 | ||||||
| 学位名の言語 | ja | |||||
| 学位名 | 博士(医学) | |||||
| 学位名 | ||||||
| 学位名の言語 | en | |||||
| 学位名 | Doctor of Philosophy in Medical Science | |||||
| 学位授与機関名 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 17701 | |||||
| 学位授与機関名の言語 | ja | |||||
| 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 | 2021-05-17 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲総研第607号 | |||||
