| Item type |
学術雑誌論文 / Journal Article_02(1) |
| 公開日 |
2009-01-19 |
| タイトル |
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タイトル |
NFAT2 IS AN ESSENTIAL MEDIATOR OF ORTHOPEDIC PARTICLE-INDUCED OSTEOCLASTOGENESIS |
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言語 |
en |
| 言語 |
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言語 |
eng |
| キーワード |
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主題Scheme |
Other |
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キーワード |
NFAT2、Osteoclast、PMMA、JNK |
| 資源タイプ |
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資源タイプ |
journal article |
| 著者 |
山中, 康裕
Abu-Amer, Wahid
Foglia, Domenica
Otero, Jesse
Clohisy, John
Abu-Amer, Yousef
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| 著者 ローマ字 |
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Yamanaka, Yasuhiro |
| 書誌情報 |
Journal of Orthopedic Research
巻 26,
号 12,
p. 1577-1584,
発行日 2008-12-01
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| DOI |
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識別子タイプ |
DOI |
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関連識別子 |
10.1002/jor.20714 |
| リンクURL |
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内容記述タイプ |
Other |
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内容記述 |
http://www.ncbi.nlm.nih.gov/pubmed?term=NFAT2%20IS%20AN%20ESSENTIAL%20MEDIATOR%20OF%20ORTHOPEDIC%20PARTICLE-INDUCED%20OSTEOCLASTOGENESIS | http://www.ncbi.nlm.nih.gov/pubmed?term=NFAT2%20IS%20AN%20ESSENTIAL%20MEDIATOR%20OF%20ORTHOPEDIC%20PARTICLE-INDUCED%20OSTEOCLASTOGENESIS |
| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Particle-induced periprosthetic osteolysis is the major cause for orthopedic implant failure. This failure is mediated mainly by the action of osteoclasts, the principal cells responsible for bone resorption and osteolysis. Therapeutic interventions to alleviate osteolysis have been focused on understanding and targeting mechanisms of osteoclastogenesis. The nuclear transcription factor NFAT is an essential terminal differentiation factor of osteoclastogenesis. This transcription factor is known to cooperate with c-jun/AP-1 in mediating RANKL-induced osteoclastogenesis. We have previously determined that RANKL is an essential cytokine mediator of particle-induced osteoclastogenesis, and that PMMA particles activate JNK and c-jun/AP-1 in bone marrow macrophages (osteoclast precursors). In the current study, we investigated the effect of PMMA particles on the NFAT signaling pathway in osteoclast precursor cells. Our findings point out that PMMA particles stimulate nuclear translocation of NFAT2 in wild-type osteoclast precursors, which is associated with increased osteoclastogenesis. More importantly, induction of osteoclastogenesis was selectively blocked in a dose-dependent fashion by the calcineurin inhibitors, Cyclosporine-A and FK506. Further, this activation was also blocked in a time-dependent fashion by the NFAT inhibitor VIVIT. Finally, we provide novel evidence that PMMA particles induce binding of NFAT2 and AP-1 proteins. Thus, our findings demonstrate that activation of the NFAT pathway in conjunction with MAP kinases is essential for basal and PMMA-stimulated osteoclastogenesis. |
| 注記 |
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内容記述タイプ |
Other |
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注記 |
Author |
| 資源タイプ |
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内容記述タイプ |
Other |
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資源タイプ |
text |
| フォーマット |
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内容記述タイプ |
Other |
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内容記述 |
application/pdf |
| ID(XooNIps) |
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18655139 |
| 閲覧数(XooNIps) |
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| ダウンロード数(XooNIps) |
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953 |
1409.pdf (1.3 MB)
