title: 5,7,3',4'-Tetramethoxyflavone exhibits chondroprotective activity by targeting β-catenin signaling in vivo and in vitro.
abstract: Osteoarthritis (OA) is a progressive joint disorder, which remains the leading cause of chronic disability in aged people. This study is the first report which demonstrates the cartilage protective effect of 5,7,3',4'-tetramethoxyflavone (TMF) by decreasing the concentration of IL-1β, TNF-α and PGE2 in the knee synovial fluid in OA rat models in vivo. In vitro, after induced by PGE2, the apoptosis rate of chondrocytes was significantly increased. In addition, PGE2 increased the expression of cAMP/PKA signaling pathway in chondrocytes, stabilized and accumulated β-catenin, and activated the expression of β-catenin signaling pathway. These activities were counteracted by TMF dose-dependently. Collectively, TMF is a potential compound with chondroprotective activity by inhibiting both EP/cAMP/PKA signaling pathway and β-catenin signaling pathway.
authors.affiliation: College of Pharmacy, Gannan Medical University, Ganzhou 341000, China. Electronic address: longhwu@hotmail.com.
authors.forename: Longhuo
authors.initials: L
authors.lastname: Wu
authors.affiliation: College of Pharmacy, Gannan Medical University, Ganzhou 341000, China.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Gannan Medical University, Ganzhou 341000, China.
authors.forename: Linfu
authors.initials: L
authors.lastname: Li
authors.affiliation: College of Pharmacy, Gannan Medical University, Ganzhou 341000, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Gannan Medical University, Ganzhou 341000, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yang
authors.affiliation: College of Pharmacy, Gannan Medical University, Ganzhou 341000, China.
authors.forename: Zhaowen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Gannan Medical University, Ganzhou 341000, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D004195:Disease Models, Animal; D005419:Flavonoids / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D008297:Male; D010003:Osteoarthritis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013582:Synovial Fluid / Q000187:drug effects* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C495268:Ctnnb1 protein, rat; D005419:Flavonoids; D051176:beta Catenin; C103111:5,7,3',4'-tetramethylluteolin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone; D047311:Luteolin
keywords: 5,7,3′,4′-Tetramethoxyflavone; Chondrocytes; Osteoarthritis; PGE(2); β-Catenin