| Project/Area Number |
15K15541
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
ASOU Yoshinori 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (50345279)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 変形性関節症 / メタボリックシンドローム / 尿酸 / キサンチンオキシダーゼ / 尿酸代謝 / 高脂肪食 / 変形性膝関節症 / 膝蓋下脂肪体 / キサンチンオキシドリダクターゼ |
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| Outline of Final Research Achievements |
A metabolic syndrome (MetS) is accompanied by hyperuricemia, during which xanthine oxidoreductase (XOR) catalyzes the production of uric acid. In the cohort study, a correlation between uric acid concentration in the synovial fluid and osteoarthritis (OA) incidence is observed. The purpose of our study was to elucidate XOR function in terms of correlation between MetS and OA. Mice were fed normal diet (ND) or high fat diet (HFD) with or without febuxostat (FEB), a XOR inhibitor. HFD stimulated XOR activity in the IPFP and the visceral fat. OA changes had progressed due to HFD, but these changes were reduced upon FEB administration. IL-1β expression in the HFD group was increased in accordance with the enhancement of NLRP3 or iNOS expression in the infrapatellar fat pad (IPFP), whereas it was inhibited by FEB administration. Based on the above results, we showed that inflammasome activation accompanied by an increase in XOR activity contributed to IFP inflammation.
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