期刊
OSTEOARTHRITIS AND CARTILAGE
卷 22, 期 1, 页码 133-144出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.joca.2013.10.016
关键词
Cannabinoid; Cartilage degradation; Chondrocytes; Interleukin 1 (IL-1); Matrix metalloproteinases (MMPs); Tissue inhibitors of matrix; metalloproteinases (TIMP)
资金
- Biomedical Research Centre, Faculty of Health and Well Being, Sheffield Hallam University, Sheffield, UK
Objective: Interleukin-1 beta (IL-1 beta) is involved in the up-regulation of matrix metalloproteinases (MMPs) leading to cartilage degradation. Cannabinoids are anti-inflammatory and reduce joint damage in animal models of arthritis. This study aimed to determine a mechanism whereby the synthetic cannabinoid WIN-55,212-2 mesylate (WIN-55) may inhibit cartilage degradation. Methods: Effects of WIN-55 were studied on IL-1 beta stimulated production of MMP-3 and -13 and their inhibitors TIMP-1 and -2 in human chondrocytes. Chondrocytes were obtained from articular cartilage of patients undergoing total knee replacement. Chondrocytes were grown in monolayer and 3D alginate bead cultures. Real-time polymerase chain reaction (PCR) was used to determine the gene expression of MMP-3, -13, TIMP-1 and -2 and Enzyme Linked Immunosorbent Assay (ELISA) to measure the amount of MMP-3 and MMP-13 protein released into media. Immunocytochemistry was used to investigate the expression of cannabinoid receptors in chondrocyte cultures. Results: Treatment with WIN-55 alone or in combination with IL-1 beta, decreased or abolished MMP-3, -13, TIMP-1 and -2 gene expression in human chondrocyte monolayer and alginate bead cultures in both a concentration and time dependent manner. WIN-55 treatment alone, and in combination with IL-1 beta, reduced MMP-3 and -13 protein production by chondrocytes cultured in alginate beads. Immunocytochemistry demonstrated the expression of cannabinoid receptors in chondrocyte cultures. Conclusion: Cannabinoid WIN-55 can reduce both basal and IL-1 beta stimulated gene and protein expression of MMP-3 and -13. However WIN-55 also decreased basal levels of TIMP-1 and -2 mRNA. These actions of WIN-55 suggest a mechanism by which cannabinoids may act to prevent cartilage breakdown in arthritis. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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