2014 Fiscal Year Final Research Report
ER stress-mediated regulation of osteoclast differentiation
| Project/Area Number |
24791566
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | 小胞体ストレス / 破骨細胞 / 骨芽細胞 |
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| Outline of Final Research Achievements |
We aimed to clarify the IRE1α-XBP1 pathway, one of the major branch of UPR pathways, in the regulation of osteoclast differentiation. First, we generated Ire1αMx1cre mice, in which the Ire1α locus can be excised in hematopoietic cells by injecting pI-pC. The analyses showed a significant increase in bone volume in Ire1αMx1cre mice compared to wild type due to a decrease in osteoclast number and activity. Next, transcriptional analysis revealed that IRE1α-deficient osteoclast precursors are defective in inducing Nfatc1, the master regulator of osteoclast differentiation. Most importantly, we found that XBP1, a transcription factor that is activated by IRE1α, binds to the promoter of Nfatc1 gene and promotes its transcription. These observations indicate that the IRE1α-XBP1 pathway is a novel regulator of Nfatc1 transcription.
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| Free Research Field |
骨代謝
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