論文 - 詳細
| RRC ID | 51599 |
|---|---|
| 著者 | Meng F, Zhang Z, Chen W, Huang G, He A, Hou C, Long Y, Yang Z, Zhang Z, Liao W. |
| タイトル | MicroRNA-320 regulates matrix metalloproteinase-13 expression in chondrogenesis and interleukin-1β-induced chondrocyte responses. |
| ジャーナル | Osteoarthritis Cartilage |
| Abstract |
OBJECTIVE:Metalloproteinases (MMPs) are key regulators of osteoarthritis (OA) and collagen degradation and have been shown to participate in endochondral ossification. The aim of this study was to determine whether microRNA-320 (miR-320) regulates the expression of MMP-13 in chondrogenesis and inflammation. EXPERIMENTAL DESIGN:miR-320 expression was assessed in vitro, in the ATDC5 cell model of chondrogenesis and in interleukin-1β (IL-1β)-treated primary mouse chondrocytes (PMCs), and in vivo, in normal and OA human cartilage by in situ hybridization. ATDC5 and PMCs were transfected with miR-320 or its antisense inhibitor (anti-miR-320), respectively. The roles of activated MAP kinases (MAPK) and NF-κB were evaluated by using specific inhibitors. Direct interaction between miR-320 and its putative binding site in the 3'-untranslated region (3'-UTR) of Mmp-13 mRNA was confirmed by the luciferase reporter assay. RESULTS:miR-320 expression was elevated in chondrogenic and hypertrophic ATDC5, while significantly reduced in OA cartilage compared with normal cartilage. Stimulation with IL-1β led to a significant reduction in miR-320 expression in PMCs. Upregulation of MMP-13 expression was correlated with downregulation of miR-320 expression in both PMCs and ATDC5. Overexpression of miR-320 suppressed the activity of a reporter construct containing the 3'-UTR and inhibited MMP-13 expression in both ATDC5 and IL-1β-treated PMCs, while treatment with anti-miR-320 enhanced MMP-13 expression. NF-κB and MAPK activation downregulated miR-320 expression. CONCLUSION:Cartilage development and homeostasis are influenced by miR-320, which directly targets MMP-13 and regulates chondrogenesis and the IL-1β-stimulated catabolic effect in mouse chondrocytes. |
| 巻・号 | 24(5) |
| ページ | 932-41 |
| 公開日 | 2016-5-1 |
| DOI | 10.1016/j.joca.2015.12.012 |
| PII | S1063-4584(15)01435-1 |
| PMID | 26774733 |
| MeSH | Aged Animals Cartilage, Articular / cytology Cell Differentiation / physiology Cells, Cultured Chondrocytes / drug effects Chondrocytes / metabolism* Chondrogenesis / genetics* Chondrogenesis / physiology Gene Expression Regulation / drug effects Gene Expression Regulation / physiology Humans Interleukin-1beta / pharmacology Matrix Metalloproteinase 13 / genetics Matrix Metalloproteinase 13 / metabolism* Mice, Inbred C57BL MicroRNAs / physiology* Middle Aged Osteoarthritis, Knee / genetics Osteoarthritis, Knee / metabolism RNA, Messenger / genetics |
| IF | 4.793 |
| 引用数 | 61 |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |