Abstract
Purpose: To investigate the therapeutic effect of glucosamine cyclohexyl ester on osteoarthritis (OA) in a rat model.Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays were used to analyze the effect of glucosamine cyclohexyl ester on changes in mRNA and protein expressions of matrix metalloproteinase and tissue inhibitor of metalloproteinases-1 in isolated rat chondrocytes, and in a rat model of OA. The rat model of OA was prepared by injecting monoiodoacetate to Sprague-Dawley rats via intra-articular route.Results: Treatment of the chondrocytes with glucosamine cyclohexyl ester for 48 h prevented interleukin-1 β (IL-1β)-mediated increases in mRNA and protein expressions in matrix metalloproteinases-1, -3 and -13, and also blocked IL-1β-induced decreases in mRNA and protein expressions of tissue inhibitor of metalloproteinase-1. Glucosamine cyclohexyl ester treatment also blocked the onset of morphological changes such as irregular surface, adhesion of tissues andpresence of osteophytes in the femoral condyle surface of the OA rats. Mankin score for control, OA and glucosamine cyclohexyl ester treatment groups were 0.98 ± 0.15, 8.35 ± 0.88 and 2.39 ± 0. 67 (p = 0.002), respectively. Treatment of OA rats with glucosamine cyclohexyl ester also inhibited increases in the activities of matrix metalloproteinases-1, -3 and -13, and decreases of tissue inhibitor of metalloproteinase-1 mRNA and protein expressions. Treatment of chondrocytes and OA rats with IL-1β caused no significant changes in the levels of H3K27 and H4K8.Conclusion: These results show that glucosamine cyclohexyl ester prevents OA by targeting the expressions of matrix metalloproteinases-1, -3 and -13 and tissue inhibitor of metalloproteinases-1.Keywords: Metalloproteinases, Interleukin, Mankin score, Osteoarthritis, Cartilage
Highlights
Osteoarthritis (OA) involves the failure of chondrocytes to function properly leading to degradation of extracellular matrix [1].Chondrocytes are involved in the synthesis of extracellular matrix molecules for maintaining the stability of the articular cartilage [2,3]
These results show that glucosamine cyclohexyl ester prevents OA by targeting the expressions of matrix metalloproteinases-1, -3 and -13 and tissue inhibitor of metalloproteinases-1
The levels of mRNA expressions of matrix metalloproteinases-1, -3 and -13 in chondrocytes were increased when the chondrocytes were cultured in presence of interleukin-1 β (IL-1β)
Summary
Osteoarthritis (OA) involves the failure of chondrocytes to function properly leading to degradation of extracellular matrix [1].Chondrocytes are involved in the synthesis of extracellular matrix molecules for maintaining the stability of the articular cartilage [2,3]. Osteoarthritis (OA) involves the failure of chondrocytes to function properly leading to degradation of extracellular matrix [1]. The function of chondrocytes is regulated by various molecules such as extracellular matrix and sulfated proteoglycans through interaction between the cells and matrix [4]. Degradation of extracellular matrix molecules and inhibition of chondrocyte viability are due to the production of oxidants and IL-1β in the activated synoviocytes and mononuclear cells [6,7]. Studies have revealed that IL-1β induces expression of matrix metalloproteinases which inhibit the production of extracellular matrix molecules in chondrocytes [8,9]. Tissue inhibitors of metalloproteinase enhance the activity of matrix metalloproteinases [10]. Disturbance in equilibrium between matrix metalloproteinases and tissue inhibitors of metalloproteinase leads to the development and progression of OA [10]
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