H-B Si1, Y Zeng2, S-Y Liu3, Z-K Zhou4, Y-N Chen5, J-Q Cheng6, Y-R Lu7, B Shen8. 1. Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China; Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, China. Electronic address: sihaibo1987@163.com. 2. Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China. Electronic address: zengyigd@126.com. 3. Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, China. Electronic address: liushuyun2010@qq.com. 4. Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China. Electronic address: zongke@126.com. 5. Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, China. Electronic address: chenyounan@scu.edu.cn. 6. Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, China. Electronic address: jqcheng@scu.edu.cn. 7. Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, China. Electronic address: luyanrong@scu.edu.cn. 8. Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China. Electronic address: shenbin_1971@163.com.
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.
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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