Elucidation of molecular mechanisms of Nrf2-mediated osteoclastogenesis and search of natural products as molecular targets
| Project/Area Number |
25462892
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Nagasaki University |
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Principal Investigator |
SAKAI Eiko 長崎大学, 医歯薬学総合研究科(歯学系), 助教 (10176612)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKUBA Takayuki 長崎大学, 医歯薬学総合研究科(歯学系), 教授 (30264055)
OKAMOTO Kuniaki 長崎大学, 医歯薬学総合研究科(歯学系), 准教授 (10311846)
NISHISHITA Kazuhisa 長崎大学, 医歯薬学総合研究科(歯学系), 助教 (20237697)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | 破骨細胞 / 酸化ストレス / 天然物 / Nrf2 / 骨代謝 / osteoclast / keap1 / NFATc1 / c-Fos |
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| Outline of Final Research Achievements |
This study investigated the role of Keap1/Nrf2 axis in the differentiation of osteoclast using wild-type, Keap1-deficient, and Nrf2-deficient mice. Keap1-deficient osteoclast precursors showed defects in osteoclastogenesis through the inhibition of phosphorylation of ERK, P38 MAPK, and JNK. Furthermore, the protein expression of NFATc1 was significantly downregulated. In contrast, Nrf2-deficient osteoclast precursors underwent enhanced osteoclastogenesis through the activation of ERK, p38 MAPK, and JNK signaling. Moreover, nuclear translocation of NFATc1 and c-Fos was increased in Nrf2-deficient osteoclast precursors. However, microcomputed tomographic analyses and histological analyses of femurs with hematoxylin-eosin staining showed no significant defects among these mice. Furthermore, we compared the inhibitory effects of cafestol and kahweol, or sanguiin H-6 and its degradation product, ellagic acid on osteoclast differentiation.
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Report
(4 results)
Research Products
(15 results)
