title: Effects of cannabinoids on nitric oxide production by chondrocytes and proteoglycan degradation in cartilage.
abstract: Cannabinoids have been reported to have anti-inflammatory effects and reduce joint damage in animal models of arthritis. This suggests a potential therapeutic role in arthritis of this group of compounds. Cannabinoids were studied to determine whether they have direct effects on chondrocyte metabolism resulting in cartilage protection. Synthetic cannabinoids, R-(+)-Win-55,212 (Win-2) and S-(-)-Win-55,212 (Win-3) and the endocannabinoid, anandamide, were investigated on unstimulated or IL-1-stimulated nitric oxide (NO) production in bovine articular chondrocytes as well as on cartilage proteoglycan breakdown in bovine nasal cartilage explants. Win-2 significantly inhibited (P < 0.05) NO production in chondrocytes at 1-10 microM concentrations. The combined CB(1) and CB(2) cannabinoid receptor antagonists, AM281 and AM630, respectively, at 100 microM did not block this effect, but instead they potentiated it. Anandamide and Win-2 (5-50 microM) also inhibited the release of sulphated glycosaminoglycans in bovine cartilage explants. The results suggest that some cannabinoids may prevent cartilage resorption, in part, by inhibiting cytokine-induced NO production by chondrocytes and also by inhibiting proteoglycan degradation.
authors.affiliation: Biomedical Research Centre, Sheffield Hallam University, Howard Street, Sheffield S11WB, UK. estery.mbvundula@student.shu.ac.uk
authors.forename: Estery C
authors.initials: EC
authors.lastname: Mbvundula
authors.forename: Rowena A D
authors.initials: RA
authors.lastname: Bunning
authors.forename: K D
authors.initials: KD
authors.lastname: Rainsford
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D048588:Benzoxazines; D002186:Cannabinoids / Q000494:pharmacology*; D002356:Cartilage / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D063388:Endocannabinoids; D007211:Indoles / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D053284:Polyunsaturated Alkamides; D011509:Proteoglycans / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology
chemical_list: D001095:Arachidonic Acids; D048588:Benzoxazines; D002186:Cannabinoids; D063388:Endocannabinoids; D007211:Indoles; D007375:Interleukin-1; D009025:Morpholines; D009281:Naphthalenes; D053284:Polyunsaturated Alkamides; D011509:Proteoglycans; D011720:Pyrazoles; D009569:Nitric Oxide; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C109925:AM 281; C094023:iodopravadoline; C078814:anandamide