title: Dynamic compression inhibits the synthesis of nitric oxide and PGE(2) by IL-1beta-stimulated chondrocytes cultured in agarose constructs.
abstract: Both mechanical loading and interleukin-1beta (IL-1beta) are known to regulate metabolic processes in articular cartilage through pathways mediated by nitric oxide ((*)NO) and PGE(2). This study uses a well-characterized model system involving isolated chondrocytes cultured in agarose constructs to test the hypothesis that dynamic compression alters the synthesis of (*)NO and PGE(2) by IL-1beta-stimulated articular chondrocytes. The data presented demonstrate for the first time that dynamic compression counteracts the effects of IL-1beta on articular chondrocytes by suppressing both (*)NO and PGE(2) synthesis. Inhibitor experiments indicated that the dynamic compression-induced inhibition of PGE(2) synthesis and stimulation of proteoglycan synthesis were (*)NO mediated, while compression-induced stimulation of cell proliferation was (*)NO independent. The inhibition of (*)NO and PGE(2) by dynamic compression is a finding of major significance that could contribute to the development of novel strategies for the treatment of cartilage-degenerative disorders.
authors.affiliation: IRC in Biomedical Materials and Medical Engineering Division, Department of Engineering, Queen Mary, University of London, Mile End Road, London, E1 4NS, United Kingdom. T.T.Chowdhury@qmw.ac.uk
authors.forename: T T
authors.initials: TT
authors.lastname: Chowdhury
authors.forename: D L
authors.initials: DL
authors.lastname: Bader
authors.forename: D A
authors.initials: DA
authors.lastname: Lee
mesh_terms: D000818:Animals; D002358:Cartilage, Articular; D002417:Cattle; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D015232:Dinoprostone / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000494:pharmacology*; D008954:Models, Biological; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000378:metabolism; D012685:Sepharose / Q000494:pharmacology; D013314:Stress, Mechanical; D013431:Sulfates / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D007375:Interleukin-1; D009573:Nitrites; D013431:Sulfates; D014316:Tritium; D009569:Nitric Oxide; D012685:Sepharose; D015232:Dinoprostone; D013936:Thymidine