| Item type |
文献 / Documents(1) |
| 公開日 |
2024-10-04 |
| アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 出版社版DOI |
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関連識別子 |
https://doi.org/10.1371/journal.pone.0009870 |
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関連名称 |
10.1371/journal.pone.0009870 |
| 出版タイプ |
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|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
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|
タイトル |
TGF-β Inhibition Restores Terminal Osteoblast Differentiation to Suppress Myeloma Growth |
| タイトル別表記 |
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その他のタイトル |
TGF-β Inhibition in Myeloma |
| 著者 |
Takeuchi, Kyoko
安倍, 正博
日浅, 雅博
Oda, Asuka
Amou, Hiroe
Kido, Shinsuke
原田, 武志
Tanaka, Osamu
三木, 浩和
中村, 信元
Nakano, Ayako
Kagawa, Kumiko
Yata, Kenichiro
Ozaki, Shuji
松本, 俊夫
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| 抄録 |
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内容記述 |
Background: Multiple myeloma (MM) expands almost exclusively in the bone marrow and generates devastating bone lesions, in which bone formation is impaired and osteoclastic bone resorption is enhanced. TGF-β, a potent inhibitor of terminal osteoblast (OB) differentiation, is abundantly deposited in the bone matrix, and released and activated by the enhanced bone resorption in MM. The present study was therefore undertaken to clarify the role of TGF-β and its inhibition in bone formation and tumor growth in MM.
Methodology/Principal Findings: TGF-β suppressed OB differentiation from bone marrow stromal cells and MC3T3-E1 preosteoblastic cells, and also inhibited adipogenesis from C3H10T1/2 immature mesenchymal cells, suggesting differentiation arrest by TGF-β. Inhibitors for a TGF-β type I receptor kinase, SB431542 and Ki26894, potently enhanced OB differentiation from bone marrow stromal cells as well as MC3T3-E1 cells. The TGF-β inhibition was able to restore OB differentiation suppressed by MM cell conditioned medium as well as bone marrow plasma from MM patients. Interestingly, TGF-β inhibition expedited OB differentiation in parallel with suppression of MM cell growth. The anti-MM activity was elaborated exclusively by terminally differentiated OBs, which potentiated the cytotoxic effects of melphalan and dexamethasone on MM cells. Furthermore, TGF-β inhibition was able to suppress MM cell growth within the bone marrow while preventing bone destruction in MM-bearing animal models.
Conclusions/Significance: The present study demonstrates that TGF-β inhibition releases stromal cells from their differentiation arrest by MM and facilitates the formation of terminally differentiated OBs, and that terminally differentiated OBs inhibit MM cell growth and survival and enhance the susceptibility of MM cells to anti-MM agents to overcome the drug resistance mediated by stromal cells. Therefore, TGF-β appears to be an important therapeutic target in MM bone lesions. |
| 書誌情報 |
en : PLOS ONE
巻 5,
号 3,
p. e9870,
発行日 2010-03-25
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| 収録物ID |
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収録物識別子タイプ |
EISSN |
|
収録物識別子 |
19326203 |
| 出版者 |
|
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出版者 |
PLOS |
| 権利情報 |
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|
権利情報 |
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| EID |
|
|
識別子 |
209846 |
| 言語 |
|
|
言語 |
eng |
pone_5_3_e9870.pdf (3.2 MB)
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