Wei Shui,
Gang Luo,
Bo Qiao,
Weidong Ni,
Shuquan Guo
Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China;
For correspondence:- Shuquan Guo
Email: shuquanguo@hotmail.com
Accepted: 14 September 2017
Published: 31 October 2017
Citation:
Shui W, Luo G, Qiao B, Ni W, Guo S.
Protective effect of glucosamine cyclohexyl ester on osteoarthritis in rat via targeting expressions of matrix metalloproteinase and tissue inhibitor of metalloproteinases-1. Trop J Pharm Res 2017; 16(10):2461-2468
doi:
10.4314/tjpr.v16i10.21
© 2017 The authors.
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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 and presence 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 ILR09;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