Intra-articular injection of microRNA-140 (miRNA-140) alleviates osteoarthritis (OA) progression by modulating extracellular matrix (ECM) homeostasis in rats
| Autor: | Yi Zeng, Z. Zhou, Bing Shen, Jing-qiu Cheng, Haibo Si, Yang Chen, S.-y. Liu, Yanrong Lu |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Cartilage Articular Male medicine.medical_specialty Biomedical Engineering Drug Evaluation Preclinical Osteoarthritis Chondrocyte Injections Intra-Articular Extracellular matrix Pathogenesis Rats Sprague-Dawley 03 medical and health sciences Young Adult Chondrocytes Rheumatology Internal medicine microRNA Matrix Metalloproteinase 13 Synovial Fluid medicine Synovial fluid Animals Homeostasis Humans Orthopedics and Sports Medicine Collagen Type II Cells Cultured Aged Aged 80 and over business.industry Cartilage Middle Aged medicine.disease Arthritis Experimental Extracellular Matrix MicroRNAs 030104 developmental biology medicine.anatomical_structure Endocrinology Gene Expression Regulation Immunology Disease Progression ADAMTS5 Protein business |
| Zdroj: | Osteoarthritis and cartilage. 25(10) |
| ISSN: | 1522-9653 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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