Cannabinoid WIN-55,212-2 mesylate inhibits interleukin-1β induced matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase expression in human chondrocytes

DUNN, S.L., WILKINSON, J.M., CRAWFORD, A., LE MAITRE, Christine and BUNNING, R.A.D. (2014). Cannabinoid WIN-55,212-2 mesylate inhibits interleukin-1β induced matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase expression in human chondrocytes. Osteoarthritis and Cartilage, 22 (1), 133-144.

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Official URL: http://dx.doi.org/10.1016/j.joca.2013.10.016
Link to published version:: 10.1016/j.joca.2013.10.016

Abstract

Objective: Interleukin-1b (IL-1b) 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-1b 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-1b, 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-1b, 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-1b 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.

Item Type: Article
Additional Information: Accepted 26 October 2013
Research Institute, Centre or Group: Biomolecular Sciences Research Centre
Identification Number: 10.1016/j.joca.2013.10.016
Depositing User: Marguerite Lyons
Date Deposited: 10 Jan 2014 11:51
Last Modified: 04 Mar 2015 16:00
URI: http://shura.shu.ac.uk/id/eprint/7601

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