| Project/Area Number |
15K11052
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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 | Showa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
井上 富雄 昭和大学, 歯学部, 教授 (70184760)
高見 正道 昭和大学, 歯学部, 教授 (80307058)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 破骨細胞 / 樹状細胞 / 細胞分化 / 振り分け / 骨代謝 / RANKL / RANK / 遺伝子発現 / IRF8 |
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| Outline of Final Research Achievements |
Interferon-regulatory factor 8 (IRF-8), a transcription factor expressed by immune cells, has an inhibitory role in osteoclast differentiation. We investigated the effects of IRF8 on inflammatory bone destruction in collagen antibody-induced arthritis (CAIA) model mice. CAIA or saline was administered to IRF8+/+ (WT) and IRF8-/- (IRF8 KO) mice by intraperitoneal injection (day 0), then LPS was injected on day 2. Rheumatoid arthritis (RA) scoring was performed daily for 32 days. Following euthanasia, bone tissues were collected and histopathological analysis assays with H&E staining were performed. RA scores and histopathological features in the CA-challenged WT mice were normal on day 32, whereas those scores were severe and histopathology results significantly abnormal in the IRF8 KO mice, including inflammatory cell infiltration and synovial hyperplasia in knee joints. These results suggest an important role for IRF8 in pathological bone destruction.
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| Academic Significance and Societal Importance of the Research Achievements |
炎症性骨疾患の制御法は、骨吸収のみ、あるいは炎症のみを抑制する方法が主流であるが、今回着目したIRF8という1分子で炎症反応と骨破壊の両方を制御できる可能性があり、独創的でかつ社会に貢献できる可能性が十分ある。現在、関節リウマチの治療薬は、非ステロイド系抗炎症薬や免疫抑制剤、生物学的製剤などが使用されているが、患者の病状から慎重に薬剤を選択する必要がある。また、免疫抑制剤は肺感染症などの合併症を発症する場合もある。以上より、IRF8を制御することで、異常な骨破壊を阻止するだけでなく、免疫系細胞の異常な活性化を阻害することが可能となり、慢性炎症を伴う関節炎の新たな治療法の開発が可能となる。
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