title: Hinokitiol reduces matrix metalloproteinase expression by inhibiting Wnt/β-Catenin signaling in vitro and in vivo.
abstract: OBJECTIVE
  In this study, we investigated the effects of hinokitiol on matrix metalloproteinase (MMP)-1, -3, -13, collagen type II (Col2a1) and β-catenin expressions in rat chondrocytes induced by interleukin-1β and in an experimental rat model induced by intra-articular injection of mono-iodoacetate (MIA) into the knee.
  
  
  METHODS
  Chondrocytes were cultured from the articular cartilage of 2-week-old rats. Passaged chondrocytes were pretreated with hinokitiol for 2h followed by co-incubation with IL-1β for 24h. Quantitative real-time polymerase chain reaction and Western blotting were used to assess the expression of MMP-1, -3, -13, Col2a1 and β-catenin. Chondrocytes were also treated with Licl, Dickkopf-1, and/or hinokitiol for 24h, the MMP-1, -3, -13 and β-catenin protein levels determined by Western blotting. The in vivo effects of hinokitiol were assessed by morphological and histological analyses following MIA injection.
  
  
  RESULTS
  Hinokitiol inhibited IL-1β-stimulated MMP-1,-3 and -13 expressions and IL-1β-induced activation of intracellular β-catenin proteins in cultured chondrocytes. In vivo, morphological and histological examinations demonstrated that hinokitiol significantly ameliorated cartilage degeneration.
  
  
  CONCLUSIONS
  Hinokitiol is an effective anti-inflammatory reagent that acts by inhibiting the Wnt/β-catenin signaling pathway and could be a promising therapeutic agent for the prevention and treatment of osteoarthritis.
authors.affiliation: Department of Orthopedics Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310000, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopedics Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310000, China.
authors.forename: Xin-die
authors.initials: XD
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310000, China.
authors.forename: Kong-he
authors.initials: KH
authors.lastname: Yang
authors.affiliation: Department of Orthopedics Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310000, China.
authors.forename: Teng-di
authors.initials: TD
authors.lastname: Fan
authors.affiliation: Department of Orthopedics Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310000, China.
authors.forename: Wei-ping
authors.initials: WP
authors.lastname: Chen
authors.affiliation: Department of Orthopedics Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310000, China.
authors.forename: Li-feng
authors.initials: LF
authors.lastname: Jiang
authors.affiliation: Department of Orthopedics Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310000, China.
authors.forename: Jia-peng
authors.initials: JP
authors.lastname: Bao
authors.affiliation: Department of Orthopedics Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310000, China. Electronic address: ldwu@yahoo.com.
authors.forename: Li-dong
authors.initials: LD
authors.lastname: Wu
authors.affiliation: Department of Orthopedics Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310000, China. Electronic address: xiongyanbear@126.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiong
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000502:physiology; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D029779:Cupressaceae / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D007717:Knee / Q000473:pathology*; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D023421:Models, Animal; D039821:Monoterpenes / Q000008:administration & dosage*; D010003:Osteoarthritis / Q000188:drug therapy* / Q000276:immunology; D008517:Phytotherapy; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction / Q000187:drug effects; D014334:Tropolone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D024043:Collagen Type II; D053583:Interleukin-1beta; D039821:Monoterpenes; D051153:Wnt Proteins; D051176:beta Catenin; D014334:Tropolone; D020782:Matrix Metalloproteinases; C009479:beta-thujaplicin
keywords: Hinokitiol; Matrix metalloproteinase; Osteoarthritis; β-catenin