OBJECTIVE:

Interleukin-1β (IL-1β) 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-1β 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 PCR was used to determine the gene expression of MMP-3, -13, TIMP-1 and -2 and ELISA to measure the amount of MMP-3 and MMP-13 protein released into media. Immunocytochemistry was used to investigate the expression ofcannabinoid receptors in chondrocytes cultures.

RESULTS:

Treatment with WIN-55 alone or in combination with IL-1β, 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-1β, reduced MMP-3 and -13 protein production by chondrocytes cultured in alginate beads. Immunocytochemisty demonstrated the expression of cannabinoid receptors in chondrocyte cultures.

CONCLUSION:

Cannabinoid WIN-55 can reduce both basal and IL-1β 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.
© 2013 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.

PMID:

 

24211233

 

[PubMed – as supplied by publisher]