title: Xanthine oxidoreductase activation is implicated in the onset of metabolic arthritis.
abstract: 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. Seven week-old male C57BL6J mice were fed normal diet (ND) or high fat diet (HFD) with or without febuxostat (FEB), a XOR inhibitor. HFD stimulated xanthine oxidase activity in the IPFP and the visceral fat. OA changes at the site of the knee joints 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 IPFP, whereas it was inhibited by FEB administration. In the organ culture system, when the IPFP was stimulated with insulin, IL-1β expression was increased in accordance with the increase of NLRP3 expression; however, they were reduced by FEB administration. Based on the above results, we showed that inflammasome activation accompanied by an increase in XOR activity contributed to IPFP inflammation followed by OA progression.
authors.affiliation: Department of Orthopedics Surgery, Tokyo Medical and Dental University 1-5-45 Yushima Bunkyo-ku Tokyo, 113-8519, Japan. Electronic address: zuliorth@tmd.ac.jp.
authors.forename: Zulipiya
authors.initials: Z
authors.lastname: Aibibula
authors.affiliation: Department of Rehabilitation Medicine, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku Tokyo, 113-8519, Japan. Electronic address: marureh@tmd.ac.jp.
authors.forename: Maierhaba
authors.initials: M
authors.lastname: Ailixiding
authors.affiliation: Division of Veterinary Surgery, Nippon Veterinary and Life Science University, 1-7-1 Sakaiminamicho Musashino-shi Tokyo, 180-8602, Japan. Electronic address: s3bam2002@yahoo.co.jp.
authors.forename: Munetaka
authors.initials: M
authors.lastname: Iwata
authors.affiliation: Department of Orthopedics Surgery, Tokyo Medical and Dental University 1-5-45 Yushima Bunkyo-ku Tokyo, 113-8519, Japan. Electronic address: bokureh@tmd.ac.jp.
authors.forename: Jinying
authors.initials: J
authors.lastname: Piao
authors.affiliation: Division of Veterinary Surgery, Nippon Veterinary and Life Science University, 1-7-1 Sakaiminamicho Musashino-shi Tokyo, 180-8602, Japan. Electronic address: hara@nvlu.ac.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hara
authors.affiliation: Department of Orthopedics Surgery, Tokyo Medical and Dental University 1-5-45 Yushima Bunkyo-ku Tokyo, 113-8519, Japan. Electronic address: okawa.orth@tmd.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okawa
authors.affiliation: Department of Orthopedics Surgery, Tokyo Medical and Dental University 1-5-45 Yushima Bunkyo-ku Tokyo, 113-8519, Japan. Electronic address: aso.orth@tmd.ac.jp.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Asou
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics; D019902:Chondrocytes / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000069465:Febuxostat / Q000494:pharmacology; D033461:Hyperuricemia / Q000150:complications / Q000378:metabolism; D058847:Inflammasomes / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010003:Osteoarthritis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D054850:Osteophyte / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013583:Synovial Membrane / Q000473:pathology; D014527:Uric Acid / Q000378:metabolism; D014968:Xanthine Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D012333:RNA, Messenger; D000069465:Febuxostat; D014527:Uric Acid; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D014968:Xanthine Dehydrogenase
keywords: Infrapatellar fat pad; Metabolic syndrome; Osteoarthritis; Xanthine oxidoreductase