title: Butein inhibits IL-1β-induced inflammatory response in human osteoarthritis chondrocytes and slows the progression of osteoarthritis in mice.
abstract: Osteoarthritis (OA) is a progressive degenerative disease characterized by irreversible articular cartilage destruction. Butein, a polyphenolic compound isolated from the stem bark of cashews and Rhus verniciflua Stokes, has been reported to have anti-inflammatory effects. This study aimed to assess the effect of butein on human OA chondrocytes and mice OA models induced by destabilization of the medial meniscus (DMM). In vitro, human OA chondrocytes were pretreated with butein at 10, 50μM and subsequently stimulated with IL-1β (10ng/ml) for 24h. Production of NO, PGE2, TNF-α and IL-6 was evaluated by the Griess reaction and ELISAs. The mRNA expression of COX-2, iNOS, TNF-α, IL-6, MMP-1, MMP-3, MMP-13, ADAMTS-4, ADAMTS-5, COL-2 and SOX-9 were measured by real-time PCR. The protein expression of COX-2, iNOS, MMP-13, COL-2, SOX-9, p65 and IκB-α were detected by Western blot. P65 nuclear translocation was detected by immunofluorescence. In vivo, the severity of OA was determined by histological analysis. We found that butein significantly inhibited the IL-1β-induced production of NO and PGE2, expression of COX-2, iNOS, TNF-α, IL-6 and MMP-13, degradation of COL-2 and SOX-9 at mRNA and protein levels as well as MMP-1, MMP-3, ADAMTS-4 and ADAMTS-5 gene expression. Furthermore, butein dramatically suppressed IL-1β-stimulated IκB-α degradation and NF-kB p65 activation. In vivo, the cartilage in butein-treated mice exhibited less Safranin O loss, cartilage erosion and lower OARSI scores. Butein also reduced subchondral bone plate thickness and alleviated synovitis. Taken together, these findings indicate that butein may be a potential agent in the treatment of OA.
authors.affiliation: Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Yonglong
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.
authors.forename: Linwei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: wys9453@126.com.
authors.forename: Yaosen
authors.initials: Y
authors.lastname: Wu
mesh_terms: D031021:Anacardium / Q000276:immunology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D047188:Chalcones / Q000627:therapeutic use*; D019902:Chondrocytes / Q000187:drug effects* / Q000502:physiology; D024043:Collagen Type II / Q000378:metabolism; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy*; D055758:SOX9 Transcription Factor / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D047188:Chalcones; D024043:Collagen Type II; D053583:Interleukin-1beta; D016328:NF-kappa B; D055758:SOX9 Transcription Factor; C040918:butein
keywords: Butein; Chondrocyte; Inflammation; NF-kB; Osteoarthritis