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Decreased DNA methylation in the promoter region of the WNT5A and GDNF genes may promote the osteogenicity of mesenchymal stem cells from patients with ossified spinal ligaments.
http://hdl.handle.net/10129/5664
http://hdl.handle.net/10129/566491464922-5d88-40ab-99c2-7452f0a470da
| 名前 / ファイル | ライセンス | アクション |
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本文 (941.2 kB)
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審査要旨 (135.9 kB)
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内容要旨 (158.4 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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| 公開日 | 2015-10-27 | |||||||
| タイトル | ||||||||
| タイトル | Decreased DNA methylation in the promoter region of the WNT5A and GDNF genes may promote the osteogenicity of mesenchymal stem cells from patients with ossified spinal ligaments. | |||||||
| 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 | |||||||
| 著者 |
Chiba, Noriyuki
× Chiba, Noriyuki
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| 著者(ヨミ) | ||||||||
| 識別子Scheme | WEKO | |||||||
| 識別子 | 16033 | |||||||
| 姓名 | チバ, ノリユキ | |||||||
| 著者別名 | ||||||||
| 識別子Scheme | WEKO | |||||||
| 識別子 | 16034 | |||||||
| 姓名 | 千葉, 紀之 | |||||||
| 著者所属 | ||||||||
| 弘前大学大学院医学研究科 | ||||||||
| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | Mesenchymal stem cells (MSCs) isolated from spinal ligaments with ectopic ossification have a pro- pensity toward the osteogenic lineage. To explore epigenetic control of the osteogenic features of MSCs, we treated MSCs obtained from the spinal ligaments of ossification of yellow ligament (OYL) Pa tients and non-OYL patients with the DNA methyltransferase inhibitor, 5-aza-20-deoxycytidine (5AdC). We compared the non-OYL groups (untreated and treated with 5AdC) with the OYL groups (untreated and treated with 5AdC) by genome-wide microarray analysis. Next, we used methylated DNA immunopre- cipitation combined with quantitative real-time PCR to assess gene methylation. Ninety-eight genes showed expression significantly increased by 5AdC treatment in MSCs from non-OYL patients but not from OYL patients. In contrast, only two genes, GDNF and WNT5A, showed significantly higher expression in OYL MSCs compared with non-OYL MSCs without 5AdC treatment. Both genes were hypermethylated in non-OYL MSCs but not in OYL MSCs. Small interfering RNA targeted to each gene decreased expression of the target gene and also several osteogenic genes. Both small interfering RNAs also suppressed the activity of alkaline phosphatase, a typical marker of osteogenesis. These results suggest that the osteo- genic features of MSCs from OYL patients are promoted by unmethylated WNT5A and GDNF genes. |
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| 内容記述 | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | 掲載誌 Journal of Pharmacological Sciences, Volume 127, Issue 4, April 2015, Pages 467–473 http://www.sciencedirect.com/science/article/pii/S1347861315000705 doi:10.1016/j.jphs.2015.03.008 |
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| 書誌情報 | p. 1-37, 発行日 2015-09-30 | |||||||
| 日本十進分類法 | ||||||||
| 主題Scheme | NDC | |||||||
| 主題 | 491.366 | |||||||
| 著者版フラグ | ||||||||
| 出版タイプ | ETD | |||||||
| その他のタイトル | ||||||||
| その他のタイトル | WNT5AとGDNFのプロモーター領域におけるDNAメチル化の減少によって脊柱靱帯骨化症患者由来の間葉系幹細胞の骨化が促進される | |||||||
| タイトル（ヨミ） | ||||||||
| その他のタイトル | WNT5A ト GDHF ノ プロモーター リョウイキ ニオケル DNA メチルカ ノ ジンタイ コッカショウ カンジャ ユライノ カンヨウ ケイ カンサイボウ ノ コッカ ガ ソクシン サレル | |||||||
| NIIサブジェクト | ||||||||
| 主題Scheme | Other | |||||||
| 主題 | 基礎医学 | |||||||
| 資源タイプ | ||||||||
| 値 | Thesis | |||||||
| 学位名 | ||||||||
| 学位名 | 博士（医学） | |||||||
| 学位授与機関 | ||||||||
| 学位授与機関名 | 弘前大学 | |||||||
| 学位授与年月日 | ||||||||
| 学位授与年月日 | 2015-09-30 | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 甲1903 | |||||||
