期刊
DRUG DESIGN DEVELOPMENT AND THERAPY
卷 13, 期 -, 页码 2009-2019出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S209694
关键词
osteoarthritis; chondrocytes apoptosis; miR-29a; Wnt/beta-catenin; Foxo3a; TMF
资金
- National Natural Science Foundation of China [81660371, 81860388, 81860261]
- Natural Science Foundation of Jiangxi Province [20161BAB215219, 20171BAB215058, 20171BAB205107]
- Jiangxi Provincial Education Department [GJJ150948, GJJ160990, GJJ170851]
- Youth Jinggang Scholar Program in Jiangxi Province
- Gannan Medical University [TD201707]
Background: miR-29a, a downstream factor of Wnt/beta-catenin signaling, promotes the activity of the Wnt/beta-catenin signaling in a positive feedback loop. Our previous work showed that 5,7,3',4'-tetramethoxyflavone (TMF), a major constituent from Murraya exotica L., exhibited chondroprotective activity by inhibiting the activity of Wnt/beta-catenin signaling. Purpose: To investigate whether TMF showed the inhibitory effects on miR-29a/beta-catenin signaling by up regulation of Foxo3a expression. Methods: Rat knee OA models were duplicated by using Hulth's method. TMF (5 mu g/mL and 20 mu g/mL) was used for administration to cultured cells, which were isolated from the rat cartilages. Analysis of chondrocytes apoptosis, gene expression, and protein expression were conducted. In addition, miR-29a mimics and pcDNA3.1(+)-Foxo3a vector were used for transfection, luciferase reporter assay for detecting the activity of Wnt/beta-catenin signaling, and co-immunoprecipitation for determining proteins interaction. Results: TMF down regulated miR-29a/beta-catenin signaling activity and cleaved caspase-3 expression and up regulated Foxo3a expression in OA rat cartilages. In vitro, miR-29a mimics down regulated the expression of Foxo3a and up regulated the activity of Wnt/beta catenin signaling and cleaved caspase-3 expression. TMF ameliorated miR-29a/beta-catenininduced chondrocytes apoptosis by up regulation of Foxo3a expression. Conclusion: TMF exhibited chondroprotective activity by up regulating Foxo3a expression and subsequently inhibiting miR-29a/Wnt/beta-catenin signaling activity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据