Xanthine oxidoreductase activation is implicated in the onset of metabolic arthritis

• Published in: Biochemical and biophysical research communications 2016-03, Vol.472 (1), p.26-32
• Main Authors: Aibibula, Zulipiya, Ailixiding, Maierhaba, Iwata, Munetaka, Piao, Jinying, Hara, Yasushi, Okawa, Atsushi, Asou, Yoshinori
• Format: Article
• Language: English
• Subjects: Adipose Tissue - drug effects; Adipose Tissue - metabolism; Animals; Apoptosis; Carrier Proteins - genetics; Chondrocytes - pathology; cohort studies; Diet, High-Fat - adverse effects; Enzyme Activation; Enzyme Inhibitors - pharmacology; Febuxostat - pharmacology; high fat diet; hyperuricemia; Hyperuricemia - complications; Hyperuricemia - metabolism; inducible nitric oxide synthase; Inflammasomes - metabolism; inflammation; Infrapatellar fat pad; insulin; interleukin-1beta; Male; males; Metabolic syndrome; Metabolic Syndrome - complications; Metabolic Syndrome - metabolism; Metabolic Syndrome - pathology; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type II - genetics; NLR Family, Pyrin Domain-Containing 3 Protein; organ culture; Osteoarthritis; Osteoarthritis - etiology; Osteoarthritis - metabolism; Osteoarthritis - pathology; Osteophyte - pathology; RNA, Messenger - genetics; RNA, Messenger - metabolism; synovial fluid; Synovial Membrane - pathology; uric acid; Uric Acid - metabolism; visceral fat; xanthine; Xanthine Dehydrogenase - antagonists & inhibitors; Xanthine Dehydrogenase - metabolism; xanthine oxidase; Xanthine oxidoreductase
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2016.02.039

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. •HFD stimulated xanthine oxidase activity in the IPFP and the visceral fat.•HFD-induced knee osteoarthritis (OA) caused by IPFP inflammation was prevented by administration of XOR inhibitor.•IL-1β expression in the IPFP was stimulated by XOR activation through NLRP3 inflammasome activation.