Dynamic mechanical compression influences nitric oxide production by articular chondrocytes seeded in agarose.
Nitric oxide (NO) has been implicated in the inhibition of cell proliferation in cytokine and lipopolysaccharide (LPS)-stimulated chondrocytes and is known to be influenced by physical forces in several tissues. In this study, a well-characterized model system utilizing bovine chondrocytes embedded in 3% agarose constructs has been used to investigate the effect of dynamic strain at 0.3, 1, or 3 Hz on NO production. LPS induced a significant increase in nitrite levels, which was reversed by both L-NAME and dexamethasone. Dynamic compressive strain produced a significant reduction in nitrite production. The effect was partially blocked by L-NAME but unaffected by dexamethasone. L-NAME also reversed dynamic compression-induced stimulation of [3H]-thymidine incorporation. NO appears to be a constituent of mechanotransduction pathways which influence proliferation of bovine chondrocytes seeded within agarose constructs. The inhibitor experiments also infer that alterations in cNOS activity primarily determine the response.
Lee
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DA
IRC in Biomedical Materials, Institute of Orthopaedics, University College London Medical School, Brockley Hill, Stanmore, Middlesex, HA7 4LP, United Kingdom.
Frean
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SP
Lees
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P
Bader
D L
DL
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004789:Enzyme Activation; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009573:Nitrites / Q000032:analysis; D012685:Sepharose; D013314:Stress, Mechanical; D013936:Thymidine / Q000378:metabolism
D008070:Lipopolysaccharides; D009573:Nitrites; D009569:Nitric Oxide; D003907:Dexamethasone; D012685:Sepharose; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D013936:Thymidine