Dynamic compression inhibits fibronectin fragment induced iNOS and COX-2 expression in chondrocyte/agarose constructs.
Mechanical loading and the fibronectin fragments (FN-fs) are known to stimulate the anabolic and catabolic processes in articular cartilage, possible through pathways mediated by *NO. This study examined the combined effects of dynamic compression and the NH(2)-hep I or COOH-hep II FN-fs on the expression levels of iNOS and COX-2 and production of *NO and PGE(2) release. Both types of fragments induced iNOS and COX-2 expression and stimulated the production of *NO release. This response was inhibited by dynamic compression. Inhibitor experiments indicated that both dynamic compression and the iNOS inhibitor were important in restoring cell proliferation and proteoglycan synthesis in the presence of the FN-fs. This is the first study which demonstrates a downregulation of the FN-f-induced iNOS and COX-2 expression by dynamic compression. The combination of mechanical and pharmacological interventions makes this study a powerful tool to examine further the interactions of biomechanics and cell signalling in osteoarthritis.
Raveenthiran
S P
SP
School of Engineering and Materials Science, Queen Mary, University of London, London, E1 4NS, UK.
Chowdhury
T T
TT
D000818:Animals; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000378:metabolism; D002417:Cattle; D049109:Cell Proliferation; D019902:Chondrocytes / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015536:Down-Regulation; D005353:Fibronectins / Q000737:chemistry*; D008954:Models, Biological; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010003:Osteoarthritis / Q000378:metabolism; D012685:Sepharose / Q000737:chemistry; D015398:Signal Transduction; D013314:Stress, Mechanical
D005353:Fibronectins; D012685:Sepharose; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2