Article ; Online: Intra-articular injection of microRNA-140 (miRNA-140) alleviates osteoarthritis (OA) progression by modulating extracellular matrix (ECM) homeostasis in rats.
2017 Volume 25, Issue 10, Page(s) 1698–1707
Abstract: Objective: Disruptions of extracellular matrix (ECM) homeostasis are key events in the pathogenesis of osteoarthritis (OA). MicroRNA-140 (miRNA-140) is expressed specifically in cartilage and regulates ECM-degrading enzymes. Our objective in this study ... ...
| Abstract | Objective: Disruptions of extracellular matrix (ECM) homeostasis are key events in the pathogenesis of osteoarthritis (OA). MicroRNA-140 (miRNA-140) is expressed specifically in cartilage and regulates ECM-degrading enzymes. Our objective in this study was to determine if intra-articular injection of miRNA-140 can attenuate OA progression in rats. Design: miRNA-140 levels in human normal and OA cartilage derived chondrocytes and synovial fluid were assessed by polymerase chain reaction (PCR). After primary human chondrocytes were transfected with miRNA-140 mimic or inhibitor, PCR and western blotting were performed to quantify Collagen II, MMP-13, and ADAMTS-5 expression. An OA model was induced surgically in rats, and subsequently treated with one single intra-articular injection of miRNA-140 agomir. At 4, 8, and 12 weeks after surgery, OA progression were evaluated macroscopically, histologically, and immunohistochemically in these rats. Results: miRNA-140 levels were significantly reduced in human OA cartilage derived chondrocytes and synovial fluid compared with normal chondrocytes and synovial fluid. Overexpressing miRNA-140 in primary human chondrocytes promoted Collagen II expression and inhibited MMP-13 and ADAMTS-5 expression. miRNA-140 levels in rat cartilage were significantly higher in the miRNA-140 agomir group than in the control group. Moreover, behavioural scores, chondrocyte numbers, cartilage thickness and Collagen II expression levels in cartilage were significantly higher, while pathological scores and MMP-13 and ADAMTS-5 expression levels were significantly lower in the miRNA-140 agomir group than in the control group. Conclusion: Intra-articular injection of miRNA-140 can alleviate OA progression by modulating ECM homeostasis in rats, and may have potential as a new therapy for OA. |
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| MeSH term(s) | ADAMTS5 Protein/biosynthesis ; ADAMTS5 Protein/genetics ; Adult ; Aged ; Aged, 80 and over ; Animals ; Arthritis, Experimental/drug therapy ; Arthritis, Experimental/metabolism ; Arthritis, Experimental/pathology ; Cartilage, Articular/metabolism ; Cartilage, Articular/pathology ; Cells, Cultured ; Chondrocytes/metabolism ; Collagen Type II/biosynthesis ; Collagen Type II/genetics ; Disease Progression ; Drug Evaluation, Preclinical/methods ; Extracellular Matrix/drug effects ; Extracellular Matrix/physiology ; Gene Expression Regulation/physiology ; Homeostasis/drug effects ; Humans ; Injections, Intra-Articular ; Male ; Matrix Metalloproteinase 13/biosynthesis ; Matrix Metalloproteinase 13/genetics ; MicroRNAs/administration & dosage ; MicroRNAs/metabolism ; MicroRNAs/pharmacology ; MicroRNAs/therapeutic use ; Middle Aged ; Osteoarthritis/drug therapy ; Osteoarthritis/metabolism ; Osteoarthritis/pathology ; Rats, Sprague-Dawley ; Synovial Fluid/metabolism ; Young Adult |
| Chemical Substances | Collagen Type II ; MIRN140 microRNA, rat ; MicroRNAs ; Mirn140 microRNA, human ; ADAMTS5 Protein (EC 3.4.24.-) ; ADAMTS5 protein, human (EC 3.4.24.-) ; Matrix Metalloproteinase 13 (EC 3.4.24.-) |
| Language | English |
| Publishing date | 2017 |
| Publishing country | England |
| Document type | Journal Article |
| ZDB-ID | 1167809-4 |
| ISSN | 1522-9653 ; 1063-4584 |
| ISSN (online) | 1522-9653 |
| ISSN | 1063-4584 |
| DOI | 10.1016/j.joca.2017.06.002 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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