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PARP Inhibitor PJ34 Suppresses Osteogenic Differentiation in Mouse Mesenchymal Stem Cells by Modulating BMP-2 Signaling Pathway
http://hdl.handle.net/10069/36037
http://hdl.handle.net/10069/36037d759d92c-e0b4-4729-9cfd-602c7a5c3ef5
名前 / ファイル | ライセンス | アクション |
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IJMS16_24820.pdf (5.4 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2015-12-11 | |||||
タイトル | ||||||
タイトル | PARP Inhibitor PJ34 Suppresses Osteogenic Differentiation in Mouse Mesenchymal Stem Cells by Modulating BMP-2 Signaling Pathway | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Differentiation | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Mesenchymal stem cells | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | PARP inhibitor | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Poly(ADP-ribosyl)ation | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Kishi, Yuta
× Kishi, Yuta× Fujihara, Hisako× Kawaguchi, Koji× Yamada, Hiroyuki× Nakayama, Ryoko× Yamamoto, Nanami× Fujihara, Yuko× Hamada, Yoshiki× Satomura, Kazuhito× Masutani, Mitsuko |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Poly(ADP-ribosyl)ation is known to be involved in a variety of cellular processes, such as DNA repair, cell death, telomere regulation, genomic stability and cell differentiation by poly(ADP-ribose) polymerase (PARP). While PARP inhibitors are presently under clinical investigation for cancer therapy, little is known about their side effects. However, PARP involvement in mesenchymal stem cell (MSC) differentiation potentiates MSC-related side effects arising from PARP inhibition. In this study, effects of PARP inhibitors on MSCs were examined. MSCs demonstrated suppressed osteogenic differentiation after 1 μM PJ34 treatment without cytotoxicity, while differentiation of MSCs into chondrocytes or adipocytes was unaffected. PJ34 suppressed mRNA induction of osteogenic markers, such as Runx2, Osterix, Bone Morphogenetic Protein-2, Osteocalcin, bone sialoprotein, and Osteopontin, and protein levels of Bone Morphogenetic Protein-2, Osterix and Osteocalcin. PJ34 treatment also inhibited transcription factor regulators such as Smad1, Smad4, Smad5 and Smad8. Extracellular mineralized matrix formation was also diminished. These results strongly suggest that PARP inhibitors are capable of suppressing osteogenic differentiation and poly(ADP-ribosyl)ation may play a physiological role in this process through regulation of BMP-2 signaling. Therefore, PARP inhibition may potentially attenuate osteogenic metabolism, implicating cautious use of PARP inhibitors for cancer treatments and monitoring of patient bone metabolism levels. | |||||
書誌情報 |
International Journal of Molecular Sciences 巻 16, 号 10, p. 24820-24838, 発行日 2015-10-19 |
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出版者 | ||||||
出版者 | Multidisciplinary Digital Publishing Institute (MDPI) | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 14220067 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.3390/ijms161024820 | |||||
権利 | ||||||
権利情報 | c 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | International Journal of Molecular Sciences, 16(10), pp.24820-24838; 2015 |