The role of xanthin oxydase in the etiology of osteoarthritis

• Project/Area Number: 15K15541
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Medical and Dental University
• 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)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥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)
• 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

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.

Research Products

• [Journal Article] Intraoperative evaluation of the effects of femoral component offset and head size on joint stability in total hip arthroplasty (2017)
  • Author(s): Jinno Tetsuya、Koga Daisuke、Asou Yoshinori、Morita Sadao、Okawa Atsushi、Muneta Takeshi
  • Journal Title: Journal of Orthopaedic Surgery Volume: 25 Issue: 1
  • DOI: 10.1177/2309499016684298
  • Peer Reviewed
• [Journal Article] Xanthine oxidoreductase activation is implicated in the onset of metabolic arthritis. (2016)
  • Author(s): Aibibula Z, Ailixiding M, Iwata M, Piao J, Hara Y, Okawa A, Asou Y.
  • Journal Title: Biochem Biophys Res Commun. Volume: 472 Issue: 1 Pages: 26-32
  • DOI: 10.1016/j.bbrc.2016.02.039
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Pleiotropic Functions of High Fat Diet in the Etiology of Osteoarthritis. (2016)
  • Author(s): Asou Y, Iwata M, Ochi H, Ailixiding M, Aibibula Z, Piao J, Jin G, Hara Y, Okawa A.
  • Journal Title: PLoS One. Volume: 11 Issue: 9 Pages: e0162794-e0162794
  • DOI: 10.1371/journal.pone.0162794
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 新規PAI-1阻害剤はマウス骨髄除去モデルにおいて骨形成を促進する (2017)
  • Author(s): Aobulikasimu Alkebaier, 金 光文, 朴 金瑛, Zulipiya Aibibula, 段 孝, 市村 敦彦, 宮田 敏男, 越智 広樹, 佐藤 信吾, 大川 淳, 麻生 義則
  • Organizer: 日本整形外科基礎学術集会
• [Presentation] 新規PAI-1阻害薬は閉経後骨粗鬆症モデルの骨密度を回復させる (2017)
  • Author(s): 金 光文, 朴 英瑛, Aobulikasimu Alkebaier, Zulipiya Aibibula, 段 孝, 市村 敦彦, 赤堀 浩司, 宮田 敏男, 越智 広樹, 佐藤 信吾, 大川 淳, 麻生 義則
  • Organizer: 日本整形外科基礎学術集会
• [Presentation] 高脂肪食誘導性変形性膝関節症におけるキサンチンオキシダーゼ（XOR）の機能解析 (2016)
  • Author(s): Zulipiya Aibibula、Maierhaba Ailixiding、朴 金瑛, 金光文、古賀 大介, 大川 淳、 麻生 義則
  • Organizer: 日本整形外科基礎学術集会
  • Place of Presentation: 福岡国際会議場（福岡県 福岡市）
  • Year and Date: 2016-10-13
• [Presentation] Xanthine oxidase inhibitor febuxostat attenuate high fat diet-induced osteoarthritis. (2016)
  • Author(s): Zulipiya Aibibula*2, Maierhaba Ailixiding*1, Jinying Piao2 , Daisuke Koga2, Atsushi Okawa2, Yoshinori Asou2
  • Organizer: annual meeting of Orthopaedic Research Society
  • Place of Presentation: フロリダ州オーランド（米国）
  • Year and Date: 2016-03-05
  • Int'l Joint Research
• [Presentation] 高脂肪食誘導性変形性膝関節症におけるキサンチンオキシダーゼ(XOR)の機能解析 (2015)
  • Author(s): 麻生 義則, Zulipiya Aibibula, Maierhaba Ailixiding, 朴 金瑛, 金 光文, 古賀 大介, 大川 淳
  • Organizer: 日本整形外科基礎学会）
  • Place of Presentation: 富山国際会議場（富山県富山市）
  • Year and Date: 2015-10-22
• [Presentation] メタボリックOAにおけるキサンチンオキシダーゼの機能解析 (2015)
  • Author(s): ゾリビア アビブラ1)、マルハバ アルシデン2)、朴金瑛1)、金光文1)、大川淳1)、麻生義則
  • Organizer: 東京骨関節フォーラム
  • Place of Presentation: 昭和大学（東京都品川区）
  • Year and Date: 2015-07-04