| Item type |
itemtype_ver1(1) |
| 公開日 |
2022-06-15 |
| タイトル |
|
|
タイトル |
Promethazine Downregulates Wnt/β-Catenin Signaling and Increases the Biomechanical Forces of the Injured Achilles Tendon in the Early Stage of Healing |
|
言語 |
en |
| 著者 |
Sakaguchi, Takefumi
Ohkawara, Bisei
Kishimoto, Yasuzumi
Miyamoto, Kentaro
Ishizuka, Shinya
Hiraiwa, Hideki
Ishiguro, Naoki
Imagama, Shiro
Ohno, Kinji
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| 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 |
| 権利 |
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言語 |
en |
|
権利情報 |
Takefumi Sakaguchi, Bisei Ohkawara, Yasuzumi Kishimoto, Kentaro Miyamoto, Shinya Ishizuka, Hideki Hiraiwa, Naoki Ishiguro, Imagama, Shiro, Ohno, Kinji. Promethazine Downregulates Wnt/β-Catenin Signaling and Increases the Biomechanical Forces of the Injured Achilles Tendon in the Early Stage of Healing. The American Journal of Sports Medicine (v.50, n.5) pp.1317-1327. Copyright © [2022] (AOSSM). DOI: [10.1177/03635465221077116]. |
| キーワード |
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主題Scheme |
Other |
|
主題 |
promethazine |
| キーワード |
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主題Scheme |
Other |
|
主題 |
Achilles tendon |
| キーワード |
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|
主題Scheme |
Other |
|
主題 |
tendon healing |
| キーワード |
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|
主題Scheme |
Other |
|
主題 |
drug repositioning |
| キーワード |
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|
主題Scheme |
Other |
|
主題 |
biomechanics of the tendon |
| 内容記述 |
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内容記述タイプ |
Abstract |
|
内容記述 |
Background: Wnt/β-catenin signaling suppresses the differentiation of cultured tenocytes, but its roles in tendon repair remain mostly elusive. No chemical compounds are currently available to treat tendon injury. Hypothesis: We hypothesized that the inhibition of Wnt/β-catenin signaling would accelerate tendon healing. Study Design: Controlled laboratory study. Methods: Tendon-derived cells (TDCs) were isolated from rat Achilles tendons. The right Achilles tendon was injured via a dermal punch, while the left tendon was sham operated. A Wnt/β-catenin inhibitor, IWR-1, and an antihistamine agent, promethazine (PH), were locally and intramuscularly injected, respectively, for 2 weeks after surgery. The healing tendons were histologically and biomechanically evaluated. Results: The amount of β-catenin protein was increased in the injured tendons from postoperative weeks 0.5 to 2. Inhibition of Wnt/β-catenin signaling by IWR-1 in healing tendons improved the histological abnormalities and decreased β-catenin, but it compromised the biomechanical properties. As we previously reported that antihistamine agents suppressed Wnt/β-catenin signaling in human chondrosarcoma cells, we examined the effects of antihistamines on TDCs. We found that a first-generation antihistamine agent, PH, increased the expression of the tendon marker genes Mkx and Tnmd in TDCs. Intramuscular injection of PH did not improve histological abnormalities, but it decreased β-catenin in healing tendons and increased the peak force and stiffness of the healing tendons on postoperative week 2. On postoperative week 8, however, the biomechanical properties of vehicle-treated tendons became similar to those of PH-treated tendons. Conclusion: IWR-1 and PH suppressed Wnt/β-catenin signaling and improved the histological abnormalities of healing tendons. IWR-1, however, compromised the biomechanical properties of healing tendons, whereas PH improved them. |
|
言語 |
en |
| 出版者 |
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出版者 |
SAGE Publications |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| 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 |
| 出版タイプ |
|
|
出版タイプ |
AM |
|
出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
| 関連情報 |
|
|
関連タイプ |
isVersionOf |
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|
識別子タイプ |
DOI |
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|
関連識別子 |
https://doi.org/10.1177/03635465221077116 |
| 収録物識別子 |
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収録物識別子タイプ |
PISSN |
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収録物識別子 |
0363-5465 |
| 書誌情報 |
en : The American Journal of Sports Medicine
巻 50,
号 5,
p. 1317-1327,
発行日 2022-04
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| ファイル公開日 |
|
|
日付 |
2022-06-15 |
|
日付タイプ |
Available |
Manuscript_20211125bw.pdf (1.8 MB)
