DUNN, Sara L., WILKINSON, Jeremy Mark, CRAWFORD, Aileen, BUNNING, Rowena A.D. and LE MAITRE, Christine L. (2016). Expression of cannabinoid receptors in human osteoarthritic cartilage: implications for future therapies. Cannabis and Cannabinoid Research, 1 (1), 3-15.
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Introduction: Cannabinoids have shown to reduce joint damage in animal models of arthritis and reduce matrix metalloproteinase expression in primary human steoarthritic (OA) chondrocytes. The actions of cannabinoids are mediated by a number of receptors, including cannabinoid receptors 1 and 2 (CB1 and CB2), Gprotein-coupled receptors 55 and 18 (GPR55 and GPR18), transient receptor potential vanilloid-1 (TRPV1), and peroxisome proliferator-activated receptors alpha and gamma (PPARa and PPARc). However, to date very few studies have investigated the expression and localization of these receptors in human chondrocytes, and expression during degeneration, and thus their potential in clinical applications is unknown. Methods: Human articular cartilage from patients with symptomatic OA was graded histologically and the expression and localization of cannabinoid receptors within OA cartilage and underlying bone were determined immunohistochemically. Expression levels across regions of cartilage and changes with degeneration were investigated. Results: Expression of all the cannabinoid receptors investigated was observed with no change with grade of degeneration seen in the expression of CB1, CB2, GPR55, PPARa, and PPARc. Conversely, the number of chondrocytes within the deep zone of cartilage displaying immunopositivity for GPR18 and TRPV1 was significantly decreased in degenerate cartilage. Receptor expression was higher in chondrocytes than in osteocytes in the underlying bone. Conclusions: Chondrocytes from OA joints were shown to express a wide range of cannabinoid receptors even in degenerate tissues, demonstrating that these cells could respond to cannabinoids. Cannabinoids designed to bind to receptors inhibiting the catabolic and pain pathways within the arthritic joint, while avoiding psychoactive effects, could provide potential arthritis therapies. Key words: articular cartilage; cannabinoid receptors; cannabinoids; osteoarthritis
|Research Institute, Centre or Group:||Biomolecular Sciences Research Centre|
|Depositing User:||Marguerite Lyons|
|Date Deposited:||22 Mar 2016 15:37|
|Last Modified:||25 Feb 2017 20:20|
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